Download 1: J Endocrinol - Functional Medicine Journal

1: J Endocrinol. 1999 Nov;163(2):207-12.
Related Articles, Links
Gymnema sylvestre stimulates insulin release in vitro by increased membrane permeability.
Persaud SJ, Al-Majed H, Raman A, Jones PM.
Physiology Division, School of Biomedical Sciences, King's College, London, UK.
To determine whether extracts of Gymnema sylvestre may have therapeutic potential for the
treatment of non-insulin-dependent diabetes mellitus (NIDDM), we examined the effects of an
alcoholic extract of G. sylvestre (GS4) on insulin secretion from rat islets of Langerhans and
several pancreatic beta-cell lines. GS4 stimulated insulin release from HIT-T15, MIN6 and
RINm5F beta-cells and from islets in the absence of any other stimulus, and GS4-stimulated
insulin secretion was inhibited in the presence of 1 mM EGTA. Blockade of voltage-operated
Ca(2+) channels with 10 microM isradipine did not significantly affect GS4-induced secretion,
and insulin release in response to GS4 was independent of incubation temperature. Examination of
islet and beta-cell integrity after exposure to GS4, by trypan blue exclusion, indicated that
concentrations of GS4 that stimulated insulin secretion also caused increased uptake of dye. Two
gymnemic acid-enriched fractions of GS4, obtained by size exclusion and silica gel
chromatography, also caused increases in insulin secretion concomitant with increased trypan blue
uptake. These results confirm the stimulatory effects of G. sylvestre on insulin release, but indicate
that GS4 acts by increasing cell permeability, rather than by stimulating exocytosis by regulated
pathways. Thus the suitability of GS4 as a potential novel treatment for NIDDM can not be
assessed by direct measurements of beta-cell function in vitro.
PMID: 10556769 [PubMed - indexed for MEDLINE]
Am J Physiol. 1998 May;274(5 Pt 2):R1324-30.
Related Articles, Links
Enhanced responses of the chorda tympani nerve to nonsugar sweeteners in the diabetic
db/db mouse.
Ninomiya Y, Imoto T, Yatabe A, Kawamura S, Nakashima K, Katsukawa H.
Department of Oral Physiology, Chemistry and Pediatric Dentistry, Asahi University School of
Dentistry, Gifu, Japan.
Genetically diabetic db/db mice show greater neural and behavioral responses to sugars than lean
control mice. The present study examined chorda tympani responses of db/db mice to nonsugar
sweeteners and their inhibition by a sweet response inhibitor, gurmarin. The results showed that
responses to sucrose, saccharin, glycine, L-alanine, and D-tryptophan, but not to D-phenylalanine,
were approximately 1.5 times greater in db/db mice than in control mice. Treatment of the tongue
with gurmarin suppressed responses to these sweeteners in db/db and control mice, but the extent
of suppression was considerably smaller in db/db mice. The magnitudes of gurmarin-sensitive
components of the response to sweeteners in db/db mice were not significantly different from
those in control mice, whereas the magnitudes of gurmarin-insensitive components in db/db mice
were about twice as large as those in control mice. These results suggest that the enhancement of
chorda tympani responses in db/db mice to sucrose and other nonsugar sweeteners may occur
through gurmarin-insensitive membrane components.
PMID: 9644046 [PubMed - indexed for MEDLINE]
J Ethnopharmacol. 1990 Oct;30(3):295-300.
Related Articles, Links
Antidiabetic effect of a leaf extract from Gymnema sylvestre in non-insulin-dependent
diabetes mellitus patients.
Baskaran K, Kizar Ahamath B, Radha Shanmugasundaram K, Shanmugasundaram ER.
Department of Biochemistry, Postgraduate Institute of Basic Medical Sciences Madras, India.
The effectiveness of GS4, an extract from the leaves of Gymnema sylvestre, in controlling
hyperglycaemia was investigated in 22 Type 2 diabetic patients on conventional oral antihyperglycaemic agents. GS4 (400 mg/day) was administered for 18-20 months as a supplement to
the conventional oral drugs. During GS4 supplementation, the patients showed a significant
reduction in blood glucose, glycosylated haemoglobin and glycosylated plasma proteins, and
conventional drug dosage could be decreased. Five of the 22 diabetic patients were able to
discontinue their conventional drug and maintain their blood glucose homeostasis with GS4 alone.
These data suggest that the beta cells may be regenerated/repaired in Type 2 diabetic patients on
GS4 supplementation. This is supported by the appearance of raised insulin levels in the serum of
patients after GS4 supplementation.
Keywords for above are: gymnema sylvestre, niddm
J Ethnopharmacol. 1990 Oct;30(3):265-79.
Related Articles, Links
Possible regeneration of the islets of Langerhans in streptozotocin-diabetic rats given
Gymnema sylvestre leaf extracts.
Shanmugasundaram ER, Gopinath KL, Radha Shanmugasundaram K, Rajendran VM.
Department of Biochemistry, University of Madras, India.
Two water soluble extracts, GS3 and GS4, obtained from the leaves of Gymnema sylvestre, were
tested in streptozotocin treated rats for their effects on blood glucose homeostasis and pancreatic
endocrine tissue. In the diabetic rats, fasting blood glucose levels returned to normal after 60 days
of GS3 and after 20 days of GS4 oral administration. Blood collected during the conduct of oral
glucose tolerance tests was used to assay for serum insulin. GS3 and GS4 therapy led to a rise in
serum insulin to levels closer to normal fasting levels. In diabetic rat pancreas, both GS3 and GS4
were able to double the islet number and beta cell number. This herbal therapy appears to bring
about blood glucose homeostasis through increased serum insulin levels provided by
repair/regeneration of the endocrine pancreas.
PMID: 2259215 [PubMed - indexed for MEDLINE]
Diabetes Res Clin Pract. 1990 May-Jun;9(2):143-8.
Related Articles, Links
Effect of Gymnema sylvestre, R.Br. on glucose homeostasis in rats.
Okabayashi Y, Tani S, Fujisawa T, Koide M, Hasegawa H, Nakamura T, Fujii M, Otsuki M.
Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
Effect of Gymnema sylvestre, R.Br. (G. sylvestre; GS4) on glucose homeostasis was studied in
rats. In the first set of experiments, the acute effect of GS4 was examined in both non-diabetic and
streptozocin (30 mg/kg)-induced mildly diabetic rats. Administration of 1 g/kg body weight of
GS4 to 18-h fasted non-diabetic rats significantly attenuated the serum glucose response to oral
administration of 1 g/kg glucose. The immunoreactive insulin (IRI) response in GS4-administered
rats was lower, but not significantly, than that in control rats. In mildly diabetic rats, a 60 min
increment in serum glucose concentrations was significantly reduced by GS4 administration. No
IRI response was observed in these diabetic rats irrespective of GS4 administration. In the second
set of experiments, the chronic effect of GS4 was examined in mildly diabetic rats. Two weeks
after the induction of diabetes, the rats were divided into two groups that had similar impairment
of glucose tolerance assessed by an oral glucose loading test. The rats were fed for 32-35 days
with either a control diet or a diet supplemented with GS4. After 4 weeks, GS4 showed a tendency
to reduce the serum glucose concentrations in the fed state and to improve the glucose tolerance.
Gain in body weight, food intake, pancreas weight and the pancreatic contents of IRI, protein,
amylase and trypsinogen were unaltered in the GS4-treated group compared with the control.
These results suggest the usefulness of G. sylvestre in the treatment of certain classes of noninsulin-dependent diabetes mellitus.
PMID: 1695875 [PubMed - indexed for MEDLINE]
Pancreas. 1991 Mar;6(2):221-8.
Related Articles, Links
Effects of leucine on insulin secretion and beta cell membrane potential in mouse islets of
Langerhans.
Brouwer AE, Carroll PB, Atwater IJ.
University of Leiden, Faculty of Medicine, The Netherlands.
Leucine is known to enhance insulin secretion from islets of Langerhans, and insulin promotes
leucine uptake in peripheral tissues. The present studies were designed to elucidate the effects of
leucine on glucose responsiveness and stimulus secretion coupling in mouse islets of Langerhans.
The effects of 20 mM leucine on insulin secretion and membrane potential were studied over a
range of glucose concentrations (0-27.7 mM). Microdissected, perifused pancreatic islets from
normal adult mice were used for both studies of insulin secretion and electrophysiology in order to
make a close comparison between these measurements. Leucine enhanced the insulin secretion in
the presence of 5.6, 11.1, and 22.2 mM glucose. In the presence of leucine, 27 mM glucose
inhibited insulin secretion. In the absence of glucose-leucine did not induce electrical activity of
the beta cell membrane, whereas in the presence of 5.6, 11.1, and 22.2 mM glucose leucine
increased spike frequency. Thus, leucine shifts both the glucose-dependent insulin secretion and
electrical activity toward lower glucose concentrations. It is concluded that leucine and glucose
share a common metabolic pathway (citric acid cycle) for stimulatory effects. Leucine is
deaminated to form 2-ketoisocaproic acid (KIC) and produce NH4+. We propose that in the
absence of glucose this increases cytosolic pH, which in turn increases K+ permeability, and
inhibits electrical activity and insulin secretion.
PMID: 1886890 [PubMed - indexed for MEDLINE]
J Endocrinol. 1989 Jun;121(3):479-85.
Related Articles, Links
Effects of islet hormones on insulin secretion from cloned B cell lines, HIT-T15 and RINm5F.
Lambert DG, Atkins TW.
Pharmaceutical Sciences Institute, Aston University, Birmingham.
The effects of the islet cell hormones glucagon, somatostatin-28 and pancreatic polypeptide on
insulin secretion from cultured cloned pancreatic B cells (HIT-T15 and RINm5F) have been
investigated. Glucagon stimulates the secretion of insulin from HIT-T15 cells in the absence and
presence of glucose and from RINm5F cells in the absence and presence of glyceraldehyde. HITT15 cells were more sensitive to the stimulatory effect of glucagon than RINm5F cells.
Somatostatin-28 and pancreatic polypeptide, both alone and in combination, reduced glucose- and
glucagon-stimulated insulin release from HIT-T15 cells and glyceraldehyde- and glucagonstimulated insulin release from RINm5F cells. HIT-T15 cells were more sensitive to the inhibitory
actions of somatostatin-28 and pancreatic polypeptide than RINm5F cells. This study supports the
hypothesis that insulin release from normal B cells may be modified by the paracrine activity of
islet hormones, glucagon, somatostatin and pancreatic polypeptide and probably occurs before any
fine tuning imposed by subsequently released insulin.
PMID: 2569024 [PubMed - indexed for MEDLINE]
Proc Natl Acad Sci U S A. 1984 Mar;81(6):1822-6.
Related Articles, Links
Bombesin stimulates insulin secretion by a pancreatic islet cell line.
Swope SL, Schonbrunn A.
The amphibian tetradecapeptide, bombesin (BBS) has been shown to stimulate insulin secretion
both in vivo and by pancreatic islet cells in vitro. To determine whether BBS can act directly on
pancreatic beta cells, we examined its effects on insulin secretion by HIT-T15 cells (HIT cells), a
clonal islet cell line. Addition of 100 nM BBS to HIT cells stimulated insulin release 25-fold
within 30 sec. The rapid stimulatory effect of BBS on insulin release was short-lived: the secretory
rate returned to basal levels after 90 min of BBS treatment. The decrease in the rate of insulin
release in the continued presence of BBS was due not to depletion of intracellular insulin stores
but to specific desensitization to this peptide. Stimulation of insulin secretion by BBS was dose
dependent with an ED50 value (0.51 +/- 0.15 nM) similar to the concentration of BBS-like
immunoreactive material in rat plasma. Five BBS analogs, including porcine gastrin-releasing
peptide, were as powerful as BBS in stimulating insulin release. The relative potencies of the
analogs tested indicated that the COOH-terminal octapeptide sequence in BBS was sufficient for
stimulation of release. In contrast, 14 peptides structurally unrelated to BBS did not alter insulin
secretion. BBS action was synergistic with that of glucagon; insulin secretion in the presence of
maximal concentrations of both peptides was greater than the additive effects of the two peptides
added individually. Somatostatin inhibited BBS-stimulated release by 69 +/- 1% with an ID50
value of 3.2 +/- 0.3 nM. These results show that BBS stimulation of insulin secretion by a clonal
pancreatic cell line closely parallels its effects in vivo and support the hypothesis that BBS
stimulates insulin secretion by a direct effect on the pancreatic beta cell. The clonal HIT cell line
provides a homogeneous cell preparation amenable for studies on the biochemical mechanisms of
BBS action in the endocrine pancreas.
PMID: 6143320 [PubMed - indexed for MEDLINE]
1: J Endocrinol. 1999 Nov;163(2):207-12.
Related Articles, Links
Gymnema sylvestre stimulates insulin release in vitro by increased membrane permeability.
Persaud SJ, Al-Majed H, Raman A, Jones PM.
Physiology Division, School of Biomedical Sciences, King's College, London, UK.
To determine whether extracts of Gymnema sylvestre may have therapeutic potential for the
treatment of non-insulin-dependent diabetes mellitus (NIDDM), we examined the effects of an
alcoholic extract of G. sylvestre (GS4) on insulin secretion from rat islets of Langerhans and
several pancreatic beta-cell lines. GS4 stimulated insulin release from HIT-T15, MIN6 and
RINm5F beta-cells and from islets in the absence of any other stimulus, and GS4-stimulated
insulin secretion was inhibited in the presence of 1 mM EGTA. Blockade of voltage-operated
Ca(2+) channels with 10 microM isradipine did not significantly affect GS4-induced secretion,
and insulin release in response to GS4 was independent of incubation temperature. Examination of
islet and beta-cell integrity after exposure to GS4, by trypan blue exclusion, indicated that
concentrations of GS4 that stimulated insulin secretion also caused increased uptake of dye. Two
gymnemic acid-enriched fractions of GS4, obtained by size exclusion and silica gel
chromatography, also caused increases in insulin secretion concomitant with increased trypan blue
uptake. These results confirm the stimulatory effects of G. sylvestre on insulin release, but indicate
that GS4 acts by increasing cell permeability, rather than by stimulating exocytosis by regulated
pathways. Thus the suitability of GS4 as a potential novel treatment for NIDDM can not be
assessed by direct measurements of beta-cell function in vitro.
PMID: 10556769 [PubMed - indexed for MEDLINE]
2: Am J Physiol. 1998 May;274(5 Pt 2):R1324-30.
Related Articles, Links
Enhanced responses of the chorda tympani nerve to nonsugar sweeteners in the diabetic
db/db mouse.
Ninomiya Y, Imoto T, Yatabe A, Kawamura S, Nakashima K, Katsukawa H.
Department of Oral Physiology, Chemistry and Pediatric Dentistry, Asahi University School of
Dentistry, Gifu, Japan.
Genetically diabetic db/db mice show greater neural and behavioral responses to sugars than lean
control mice. The present study examined chorda tympani responses of db/db mice to nonsugar
sweeteners and their inhibition by a sweet response inhibitor, gurmarin. The results showed that
responses to sucrose, saccharin, glycine, L-alanine, and D-tryptophan, but not to D-phenylalanine,
were approximately 1.5 times greater in db/db mice than in control mice. Treatment of the tongue
with gurmarin suppressed responses to these sweeteners in db/db and control mice, but the extent
of suppression was considerably smaller in db/db mice. The magnitudes of gurmarin-sensitive
components of the response to sweeteners in db/db mice were not significantly different from
those in control mice, whereas the magnitudes of gurmarin-insensitive components in db/db mice
were about twice as large as those in control mice. These results suggest that the enhancement of
chorda tympani responses in db/db mice to sucrose and other nonsugar sweeteners may occur
through gurmarin-insensitive membrane components.
PMID: 9644046 [PubMed - indexed for MEDLINE]
3: J Ethnopharmacol. 1990 Oct;30(3):295-300.
Related Articles, Links
Antidiabetic effect of a leaf extract from Gymnema sylvestre in non-insulin-dependent
diabetes mellitus patients.
Baskaran K, Kizar Ahamath B, Radha Shanmugasundaram K, Shanmugasundaram ER.
Department of Biochemistry, Postgraduate Institute of Basic Medical Sciences Madras, India.
The effectiveness of GS4, an extract from the leaves of Gymnema sylvestre, in controlling
hyperglycaemia was investigated in 22 Type 2 diabetic patients on conventional oral antihyperglycaemic agents. GS4 (400 mg/day) was administered for 18-20 months as a supplement to
the conventional oral drugs. During GS4 supplementation, the patients showed a significant
reduction in blood glucose, glycosylated haemoglobin and glycosylated plasma proteins, and
conventional drug dosage could be decreased. Five of the 22 diabetic patients were able to
discontinue their conventional drug and maintain their blood glucose homeostasis with GS4 alone.
These data suggest that the beta cells may be regenerated/repaired in Type 2 diabetic patients on
GS4 supplementation. This is supported by the appearance of raised insulin levels in the serum of
patients after GS4 supplementation.
Publication Types:

Clinical Trial
PMID: 2259217 [PubMed - indexed for MEDLINE]
4: J Ethnopharmacol. 1990 Oct;30(3):265-79.
Related Articles, Links
Possible regeneration of the islets of Langerhans in streptozotocin-diabetic rats given
Gymnema sylvestre leaf extracts.
Shanmugasundaram ER, Gopinath KL, Radha Shanmugasundaram K, Rajendran VM.
Department of Biochemistry, University of Madras, India.
Two water soluble extracts, GS3 and GS4, obtained from the leaves of Gymnema sylvestre, were
tested in streptozotocin treated rats for their effects on blood glucose homeostasis and pancreatic
endocrine tissue. In the diabetic rats, fasting blood glucose levels returned to normal after 60 days
of GS3 and after 20 days of GS4 oral administration. Blood collected during the conduct of oral
glucose tolerance tests was used to assay for serum insulin. GS3 and GS4 therapy led to a rise in
serum insulin to levels closer to normal fasting levels. In diabetic rat pancreas, both GS3 and GS4
were able to double the islet number and beta cell number. This herbal therapy appears to bring
about blood glucose homeostasis through increased serum insulin levels provided by
repair/regeneration of the endocrine pancreas.
PMID: 2259215 [PubMed - indexed for MEDLINE]
5: Diabetes Res Clin Pract. 1990 May-Jun;9(2):143-8.
Related Articles, Links
Effect of Gymnema sylvestre, R.Br. on glucose homeostasis in rats.
Okabayashi Y, Tani S, Fujisawa T, Koide M, Hasegawa H, Nakamura T, Fujii M, Otsuki M.
Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
Effect of Gymnema sylvestre, R.Br. (G. sylvestre; GS4) on glucose homeostasis was studied in
rats. In the first set of experiments, the acute effect of GS4 was examined in both non-diabetic and
streptozocin (30 mg/kg)-induced mildly diabetic rats. Administration of 1 g/kg body weight of
GS4 to 18-h fasted non-diabetic rats significantly attenuated the serum glucose response to oral
administration of 1 g/kg glucose. The immunoreactive insulin (IRI) response in GS4-administered
rats was lower, but not significantly, than that in control rats. In mildly diabetic rats, a 60 min
increment in serum glucose concentrations was significantly reduced by GS4 administration. No
IRI response was observed in these diabetic rats irrespective of GS4 administration. In the second
set of experiments, the chronic effect of GS4 was examined in mildly diabetic rats. Two weeks
after the induction of diabetes, the rats were divided into two groups that had similar impairment
of glucose tolerance assessed by an oral glucose loading test. The rats were fed for 32-35 days
with either a control diet or a diet supplemented with GS4. After 4 weeks, GS4 showed a tendency
to reduce the serum glucose concentrations in the fed state and to improve the glucose tolerance.
Gain in body weight, food intake, pancreas weight and the pancreatic contents of IRI, protein,
amylase and trypsinogen were unaltered in the GS4-treated group compared with the control.
These results suggest the usefulness of G. sylvestre in the treatment of certain classes of noninsulin-dependent diabetes mellitus.
PMID: 1695875 [PubMed - indexed for MEDLINE]
6: Phytomedicine. 2002 May;9(4):346-51.
Related Articles, Links
Extract of Ocimum canum lowers blood glucose and facilitates insulin release by isolated
pancreatic beta-islet cells.
Nyarko AK, Asare-Anane H, Ofosuhene M, Addy ME.
Noguchi Memorial Institute for Medical Research, University of Ghana, Legon.
[email protected]
Aqueous extract of Ocimum canum Sim, (Lamiaceae) is used by some Ghanaians to manage
diabetes mellitus. In vivo modulation of levels of fasting blood glucose by 0. canum extract was
evaluated in type-II diabetes mellitus using the C57BL/KsJ db/db genetically diabetic animal
model, and its effects on glucose-stimulated insulin release in vitro were monitored using isolated
rat pancreatic beta-islet cells. The results showed that fasting blood glucose levels and body
weight decreased significantly (p < 0.05) in diabetic and non-diabetic C57BL/KsJ mice, which
were administered aqueous extract of 0. canum. In vitro, the 0. canum extract significantly
enhanced insulin release from isolated rat pancreatic beta-islet cells. Insulin release was found to
be dependent on glucose concentration and increased with increasing O. canum concentration in
the incubation medium up to an optimum extract concentration of 0.03 mg/ml. Release of the
hormone decreased beyond this concentration of extract in the medium. Addition to the medium of
Desmodium adscendens, a plant preparation used to manage inflammatory disorders, did not
increase but rather inhibited insulin secretion by the pancreatic beta-islet cells. These results could
explain the use of 0. canum in Ghanaian folk medicine to manage diabetes mellitus.
PMID: 12120816 [PubMed - indexed for MEDLINE]
7: Diabetes. 2003 Feb;52(2):356-64.
Related Articles, Links
Stimulation of insulin secretion by denatonium, one of the most bitter-tasting substances
known.
Straub SG, Mulvaney-Musa J, Yajima H, Weiland GA, Sharp GW.
Department of Molecular Medicine, College of Veterinary Medicine, Cornell University, Ithaca,
New York 14853, USA.
Denatonium, one of the most bitter-tasting substances known, stimulated insulin secretion in
clonal HIT-T15 beta-cells and rat pancreatic islets. Stimulation of release began promptly after
exposure of the beta-cells to denatonium, reached peak rates after 4-5 min, and then declined to
near basal values after 20-30 min. In islets, no effect was observed at 2.8 mmol/;l glucose, whereas
a marked stimulation was observed at 8.3 mmol/;l glucose. No stimulation occurred in the absence
of extracellular Ca(2+) or in the presence of the Ca(2+)-channel blocker nitrendipine. Stimulated
release was inhibited by alpha(2)-adrenergic agonists. Denatonium had no direct effect on voltagegated calcium channels or on cyclic AMP levels. There was no evidence for the activation of
gustducin or transducin in the beta-cell. The results indicate that denatonium stimulates insulin
secretion by decreasing KATP channel activity, depolarizing the beta-cell, and increasing Ca(2+)
influx. Denatonium did not displace glybenclamide from its binding sites on the sulfonylurea
receptor (SUR). Strikingly, it increased glybenclamide binding by decreasing the K(d). It is
concluded that denatonium, which interacts with K(+) channels in taste cells, most likely binds to
and blocks Kir6.2. A consequence of this is a conformational change in SUR to increase the
SUR/glybenclamide binding affinity.
PMID: 12540608 [PubMed - indexed for MEDLINE]
8: Diabetologia. 1989 Jun;32(6):354-9.
Related Articles, Links
The hypoglycaemic and insulinotropic activity of Tinospora crispa: studies with human and
rat islets and HIT-T15 B cells.
Noor H, Hammonds P, Sutton R, Ashcroft SJ.
Nuffield Department of Clinical Biochemistry, John Radcliffe Hospital, Headington, Oxford, UK.
In Malaysia, Tinospora crispa extract is taken orally by Type 2 (non-insulin-dependent) diabetic
patients to treat hyperglycaemia. We have evaluated the claimed hypoglycaemic property by
adding aqueous extract to the drinking water of normal and alloxan-diabetic rats. After one week,
fasting blood glucose levels were significantly (p less than 0.01) lower and serum insulin levels
were significantly (p less than 0.01) higher in treated diabetic animals (10.4 +/- 1.0 mmol/l and
12.8 +/- 1.1 muU/ml respectively) compared to untreated diabetic controls (17.4 +/- 1.7 mmol/l
and 8.0 +/- 0.7 muU/ml respectively). The insulinotropic action of T. crispa was further
investigated in vitro using isolated human or rat islets of Langerhans and HIT-T15 cells. In static
incubations with rat islets and HIT-T15 B cells, the extract induced a dosage dependent
stimulation and potentiation of basal and glucose-stimulated insulin secretion respectively. This
insulinotropic effect was also evident in perifused human and rat islets and HIT-T5 B-cells. The
observations that (i) in all three models insulin secretory rates rapidly returned to basal levels on
removal of the extract and (ii) in rat islets, a second challenge with T. crispa induced an additional,
stimulated response, are all consistent with physiological release of insulin by B cells. Moreover,
the rate of HIT-T15 glucose utilisation was not affected by incubation with T. crispa, suggesting
that the cells were viable throughout. These are the first studies to provide biochemical evidence
which substantiates the traditional claims for an oral hypoglycaemic effect of Tinospora crispa,
and which also show that the hypoglycaemic effect is associated with increased insulin secretion.
PMID: 2668082 [PubMed - indexed for MEDLINE]
9: J Ethnopharmacol. 2002 Aug;81(3):317-20.
Related Articles, Links
Glucose lowering effect of aqueous extract of Enicostemma littorale Blume in diabetes: a
possible mechanism of action.
Maroo J, Vasu VT, Aalinkeel R, Gupta S.
Department of Biochemistry, Faculty of Science, M. S. University, Baroda Gujarat 390 002, India.
Diabetes mellitus is a chronic metabolic disorder characterized by hyperglycemia. Enicostemma
littorale Blume is a small herb and recently we have reported its blood glucose lowering potential
in alloxan induced diabetic rats. A single dose of aqueous extract of E. littorale (15 g dry plant
equivalent extract per kg) had shown significant increase in the serum insulin levels in alloxaninduced diabetic rats at 8 h. The insulinotropic action of aqueous extract of E. littorale was further
investigated using rat pancreatic islets. Extract has the potential to enhance glucose-induced
insulin release at 11.1 mM glucose from isolated rat pancreatic islets and was partially able to
reverse the effect of diazoxide (0.25 mM). Incubation with Ca(2+) chelator (EGTA) and Ca(2+)
channel blocker (nimodipine) did not affect the glucose-induced insulin release augmented by the
extract. Above results suggest the glucose lowering effect of aqueous extract of E. littorale to be
associated with potentiation of glucose-induced insulin release through K(+)-ATP channel
dependent pathway but did not require Ca(2+) influx.
PMID: 12127231 [PubMed - indexed for MEDLINE]
10: J Nutr. 1992 Dec;122(12):2367-73.
Related Articles, Links
An extract of Gymnema sylvestre leaves and purified gymnemic acid inhibits glucosestimulated gastric inhibitory peptide secretion in rats.
Fushiki T, Kojima A, Imoto T, Inoue K, Sugimoto E.
Department of Food Science and Technology, Faculty of Agriculture, Kyoto University, Japan.
Gastric inhibitory peptide release into the portal vein in response to duodenal infusion of Dglucose was studied in the presence of a leaf extract of Gymnema sylvestre, purified gymnemic
acid and inhibitors of some putative glucose sensors and carriers in the intestinal lumen.
Intraduodenal infusion of D-glucose significantly increased the portal immunoreactive gastric
inhibitory peptide concentration in a dose-dependent manner. The increase in the portal
immunoreactive gastric inhibitory peptide induced by glucose was significantly depressed by
concomitantly infused leaf extract of Gymnema sylvestre, purified gymnemic acid and phlorizin
but not by cytochalasin B. Mannoheptulose, which inhibits glycolysis, and procaine and lidocaine,
which inhibit the vagal glucoreceptor in the lumen, did not affect portal immunoreactive gastric
inhibitory peptide concentrations. These results suggest that a glucose receptor, which interacts
with the leaf extract of Gymnema sylvestre, purified gymnemic acid and phlorizin, exists for the
release of immunoreactive gastric inhibitory peptide and that the glucose receptor for gastric
inhibitory peptide release is not likely to be identical with a glucose transporter or a vagal
glucoreceptor in the lumen.
PMID: 1453221 [PubMed - indexed for MEDLINE]
11: Diabetes. 2002 Dec;51(12):3450-60.
Related Articles, Links
Exogenous nitric oxide and endogenous glucose-stimulated beta-cell nitric oxide augment
insulin release.
Smukler SR, Tang L, Wheeler MB, Salapatek AM.
Department of Physiology, University of Toronto, 1 King's College Circle, Toronto, Ontario,
Canada M5S 1A8.
The role nitric oxide (NO) plays in physiological insulin secretion has been controversial. Here we
present evidence that exogenous NO stimulates insulin secretion, and that endogenous NO
production occurs and is involved in the regulation of insulin release. Radioimmunoassay
measurement of insulin release and a dynamic assay of exocytosis using the dye FM1-43
demonstrated that three different NO donors-hydroxylamine (HA), sodium nitroprusside, and 3morpholinosydnonimine (SIN-1)-each stimulated a marked increase in insulin secretion from INS1 cells. Pharmacological manipulation of the guanylate cyclase/guanosine 3',5'-cyclic
monophosphate pathway indicated that this pathway was involved in mediating the effect of the
intracellular NO donor, HA, which was used to simulate endogenous NO production. This effect
was further characterized as involving membrane depolarization and intracellular Ca(2+)
([Ca(2+)](i)) elevation. SIN-1 application enhanced glucose-induced [Ca(2+)](i) responses in
primary beta-cells and augmented insulin release from islets in a glucose-dependent manner. Realtime monitoring of NO using the NO-sensitive fluorescent dye, diaminofluorescein, was used to
provide direct and dynamic imaging of NO generation within living beta-cells. This showed that
endogenous NO production could be stimulated by elevation of [Ca(2+)](i) levels and by glucose
in both INS-1 and primary rat beta-cells. Scavenging endogenously produced NO-attenuated
glucose-stimulated insulin release from INS-1 cells and rat islets. Thus, the results indicated that
applied NO is able to exert an insulinotropic effect, and implicated endogenously produced NO in
the physiological regulation of insulin release.
PMID: 12453899 [PubMed - indexed for MEDLINE]
12: J Biol Chem. 1994 Jan 14;269(2):1041-5.
Related Articles, Links
Ascorbic acid and insulin secretion in pancreatic islets.
Bergsten P, Moura AS, Atwater I, Levine M.
Laboratory of Cell Biology and Genetics, National Institute of Diabetes, Digestive, and Kidney
Diseases, National Institutes of Health, Bethesda, Maryland 20892.
The effect of ascorbic acid on glucose-induced insulin release from single pancreatic islets was
measured using a new, ultra-sensitive enzyme-linked immunosorbent insulin assay. Within 20 s
ascorbic acid inhibited insulin secretion; inhibition was dose dependent and completely reversible.
There was a 50% inhibition of the secretory response with 200 microM ascorbic acid and 90%
inhibition with 400 microM ascorbic acid. The decrease in insulin secretion was recorded as a
reduction of the amplitudes of the fast insulin transients, which give rise to the oscillatory nature
of insulin secretion. The inhibition of glucose-induced insulin release by ascorbic acid was
associated with hyperpolarization of the pancreatic beta-cell. Suppression of glucose-induced
membrane depolarization was evident after 20 s, was dose dependent, and was completely
reversible. The data here may provide the first explanation of why plasma ascorbate
concentrations are tightly controlled.
PMID: 8288558 [PubMed - indexed for MEDLINE]
13: Pancreas. 1997 Jul;15(1):69-77.
Related Articles, Links
Vitamin A stimulation of insulin secretion: effects on transglutaminase mRNA and activity
using rat islets and insulin-secreting cells.
Driscoll HK, Adkins CD, Chertow TE, Cordle MB, Matthews KA, Chertow BS.
Medical Service, VA Medical Center, Huntington, West Virginia, USA.
Retinol or retinoic acid is required for insulin release. Retinoids increase transglutaminase activity,
and transglutaminase has been implicated in islet insulin release. To examine whether
transglutaminase could mediate effects of retinoids on insulin secretion, we measured (i)
transglutaminase activity in islets from rats deficient in vitamin A or repleted with retinol or
retinoic acid, (ii) transglutaminase activity in RINm5F and INS-1 insulin-secreting cells cultured
in retinol or retinoic acid, (iii) mRNA for transglutaminase in RINm5F and INS-1 cells, and (iv)
insulin secretion from INS-1 cells in response to retinoic acid. Islets from rats repleted with retinol
or retinoic acid showed more than twice the transglutaminase activity of islets from vitamin A
deficient rats. Retinoic acid increased RINm5F cells and INS-1 cell transglutaminase activity.
Retinol did not increase transglutaminase activity. Transglutaminase mRNA was detected in INS1 cells but not in RINm5F cells. Retinoic acid increased insulin secretion from INS-1 cells as
observed previously in RINm5F cells. In conclusion, retinoic acid increases transglutaminase
activity in both rat islets and two insulin-secreting from INS-1 cells. Transglutaminase is a
candidate for mediating retinoid-induced changes in insulin secretion.
PMID: 9211495 [PubMed - indexed for MEDLINE]
14: Acta Biol Med Ger. 1982;41(12):1229-40.
Related Articles, Links
The insulin-releasing activity of the tropical plant momordica charantia.
Welihinda J, Arvidson G, Gylfe E, Hellman B, Karlsson E.
An aqueous extract from the unripe fruits of the tropical plant Momordica charantia was found to
be a potent stimulator of insulin release from beta-cell-rich pancreatic islets isolated from obesehyperglycemic mice. The stimulation of insulin release was partially reversible. It differed from
that of D-glucose and other commonly employed insulin secretagogues in not being suppressed by
L-epinephrine and in even being potentiated by the removal of Ca2+. This anomalous behaviour
was not associated with general effects on the metabolism of the beta-cells as indicated by an
unaltered oxidation of D-glucose. Studies of 45Ca fluxes suggest that the insulin-releasing action
is the result of perturbations of membrane functions. In support for the idea of direct effects on
membrane lipids, the action of the extract was found to mimic that of saponin in inhibiting the
Ca2+/H+ exchange mediated by the ionophore A23187 in isolated chromaffin granules and
release Ca2+ from preloaded liposomes.
PMID: 6765165 [PubMed - indexed for MEDLINE]
15: Am J Physiol Endocrinol Metab. 2001 Nov;281(5):E1082-7.
Related Articles, Links
Chronic exposure to high leucine impairs glucose-induced insulin release by lowering the
ATP-to-ADP ratio.
Anello M, Ucciardello V, Piro S, Patane G, Frittitta L, Calabrese V, Giuffrida Stella AM,
Vigneri R, Purrello F, Rabuazzo AM.
Institute of Internal Medicine, Endocrinology, and Metabolism and S. Signorelli Diabetes Center,
Ospedale Garibaldi, Italy. [email protected]
Exposure of rat pancreatic islets to 20 mM leucine for 24 h reduced insulin release in response to
glucose (16.7 and 22.2 mM). Insulin release was normal when the same islets were stimulated
with leucine (40 mM) or glyburide (1 microM). To investigate the mechanisms responsible for the
different effect of these secretagogues, we studied several steps of glucose-induced insulin
secretion. Glucose utilization and oxidation rates in leucine-precultured islets were similar to those
of control islets. Also, the ATP-sensitive K(+) channel-independent pathway of glucosestimulated insulin release, studied in the presence of 30 mM K(+) and 250 microM diazoxide, was
normal. In contrast, the ATP-to-ADP ratio after stimulation with 22.2 mM glucose was reduced in
leucine-exposed islets with respect to control islets. The decrease of the ATP-to-ADP ratio was
due to an increase of ADP levels. In conclusion, prolonged exposure of pancreatic islets to high
leucine levels selectively impairs glucose-induced insulin release. This secretory abnormality is
associated with (and might be due to) a reduced ATP-to-ADP ratio. The abnormal plasma amino
acid levels often present in obesity and diabetes may, therefore, affect pancreatic islet insulin
secretion in these patients.
PMID: 11595666 [PubMed - indexed for MEDLINE]
16: Planta Med. 2000 Jun;66(5):418-23.
Related Articles, Links
Insulinotropic effect of Citrullus colocynthis fruit extracts.
Nmila R, Gross R, Rchid H, Roye M, Manteghetti M, Petit P, Tijane M, Ribes G, Sauvaire Y.
Laboratoire de Recherche sur les Substances Naturelles Vegetales (UPRES EA 1677), Universite
Montpellier II, France.
Infusions of Citrullus colocynthis Schrad. (Cucurbitaceae) fruits are traditionally used as
antidiabetic medication in Mediterranean countries, but to our knowledge no studies have been
undertaken so far to determine the possible mechanisms involved in the antidiabetic properties of
the fruit. The present study was designed to investigate whether these fruits possess insulinotropic
effects. For this purpose, different extracts of Citrullus colocynthis seed components were
obtained: RN II (crude extract), RN VI (hydro-alcoholic extract), RN X (purified extract) and RN
XVII (beta-pyrazol-1-ylalanine), the major free amino acid present in the seeds. The insulin
secretory effects of these different extracts were evaluated in vitro in the isolated rat pancreas and
isolated rat islets in the presence of 8.3 mM glucose. All tested extracts, when perfused for 20 min
at 0.1 mg/ml, immediately and significantly stimulated insulin secretion. This effect was transient.
In addition, the purified extract (RN X) provoked a clear dose-dependent increase in insulin
release from isolated islets. Moreover, a significant and persistant increase in pancreatic flow rate
appeared during RN VI, RN X and RN XVII perfusions. In conclusion, our results show that
different Citrullus colocynthis seed extracts have an insulinotropic effect which could at least
partially account for the antidiabetic activities of these fruits.
PMID: 10909260 [PubMed - indexed for MEDLINE]
17: Obes Res. 2000 Sep;8(6):475-80.
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Augmented insulinotropic action of arachidonic acid through the lipoxygenase pathway in
the obese Zucker rat.
Ahren B, Magrum LJ, Havel PJ, Greene SF, Phinney SD, Johnson PR, Stern JS.
Department of Medicine, Lund University, Malmo, Sweden. [email protected]
OBJECTIVE: The metabolism of arachidonic acid (AA) has been shown to be altered in severe
insulin resistance that is present in obese (fa/fa) Zucker rats. We examined the effects and
mechanism of action of AA on basal and glucose-stimulated insulin secretion in pancreatic islets
isolated from obese (fa/fa) Zucker rats and their homozygous lean (Fa/Fa) littermates.
RESEARCH METHODS AND PROCEDURES: Islets were isolated from 10- to 12-week-old rats
and incubated for 45 minutes in glucose concentrations ranging from 3.3 to 16.7 mM with or
without inhibitors of the cyclooxygenase or lipoxygenase pathways. Medium insulin
concentrations were measured by radioimmunoassay, and islet production of the 12-lipoxygenase
metabolite, 12-hydroxyeicosatetraenoic acid (12-HETE), was measured by enzyme immunoassay.
RESULTS: In islets from lean animals, AA stimulated insulin secretion at submaximally
stimulatory glucose levels (<11.1 mM) but not at 16.7 mM glucose. In contrast, in islets derived
from obese rats, AA potentiated insulin secretion at all glucose concentrations. AA-induced
insulin secretion was augmented in islets from obese compared with lean rats at high
concentrations of AA in the presence of 3.3 mM glucose. Furthermore, the inhibitor of 12lipoxygenase, esculetin (0.5 microM), inhibited AA-stimulated insulin secretion in islets from
obese but not lean rats. Finally, the islet production of the 12-HETE was markedly enhanced in
islets from obese rats, both in response to 16.7 mM glucose and to AA. DISCUSSION: The
insulin secretory response to AA is augmented in islets from obese Zucker rats by a mechanism
related to enhanced activity of the 12-lipoxygenase pathway. Therefore, augmented action of AA
may be a mechanism underlying the adaptation of insulin secretion to the increased demand
caused by insulin resistance in these animals.
PMID: 11011915 [PubMed - indexed for MEDLINE]
18: Tidsskr Nor Laegeforen. 2000 Sep 30;120(23):2796-8.
Related Articles, Links
[Why is insulin release from beta cells insufficient in type 2 diabetes?]
[Article in Norwegian]
Grill V.
Institutt for abdominale fag, Regionsykehuset i Trondheim. [email protected]
Insulin secretion is finely tuned to tissue requirements by tight links to prevailing blood glucose
levels. The normal regulation of insulin secretion is linked to glucose metabolism in the pancreatic
beta-cell, a major but not exclusive signal for secretion being closure of K+ ATP-dependent
channels in the cell membrane through an increase in the cytosolic ATP/ADP. Insulin secretion in
type 2 diabetes is abnormal in several respects, due to genetic causes, but also due to the metabolic
environment of the pancreatic beta-cells. This environment may be particularly important for the
deterioration of insulin secretion, which occurs with increasing duration of diabetes. Factors of the
environment with potential importance include over-stimulation, a negative effect of
hyperglycaemia per se ("glucotoxicity"), and adverse effects of elevated fatty acids ("lipotoxicity").
A better understanding of the mechanisms behind these factors and of their clinical importance
will pave the way for treatment which could preserve beta-cell function in type 2 diabetic patients.
Publication Types:


Review
Review, Tutorial
PMID: 11107928 [PubMed - indexed for MEDLINE]
19: J Ethnopharmacol. 1998 Aug;62(1):7-13.
Related Articles, Links
Pharmacological characterisation of the antihyperglycaemic properties of Tinospora crispa
extract.
Noor H, Ashcroft SJ.
Nuffield Department of Clinical Biochemistry, John Radcliffe Hospital, Headington, Oxford, UK.
The efficacy of Tinospora crispa (Menispermaceae) extract for the treatment of diabetes has
previously been verified in animal models. In order to substantiate the antidiabetic effect, we
characterised the antihyperglycaemic properties by studying its effect on intestinal glucose
absorption and glucose uptake into adipocytes. We also performed experiments to characterise in
more detail the mechanism of T. crispa-evoked insulin release by challenging it with insulin
secretory antagonists viz. adrenaline, somatostatin, verapamil and nifedipine. In addition, we also
performed experiments to determine the effect of the extract on cAMP content. The results clearly
showed that the antihyperglycaemic effect is not due to interference with intestinal glucose uptake
or uptake of the sugar into the peripheral cells. Rather, the antihyperglycaemic effect of T. crispa
is probably due to stimulation of insulin release via modulation of beta-cell Ca2+ concentration.
That the insulinotropic effect of T. crispa is physiological suggests that the extract contains
compounds which could be purified for use in the treatment of type II diabetes.
PMID: 9720606 [PubMed - indexed for MEDLINE]
20: Br J Nutr. 1997 Aug;78(2):325-34.
Related Articles, Links
Pancreatic and extra-pancreatic effects of the traditional anti-diabetic plant, Medicago
sativa (lucerne).
Gray AM, Flatt PR.
School of Biomedical Sciences, University of Ulster, Coleraine.
Medicago sativa (lucerne) is used as a traditional plant treatment of diabetes. In the present study,
administration of lucerne in the diet (62.5 g/kg) and drinking water (2.5 g/l) reduced the
hyperglycaemia of streptozotocin-diabetic mice. An aqueous extract of lucerne (1 mg/ml)
stimulated 2-deoxy-glucose transport (1.8-fold), glucose oxidation (1.7-fold) and incorporation of
glucose into glycogen (1.6-fold) in mouse abdominal muscle. In acute 20 min tests, 0.25-1 mg/ml
aqueous extract of lucerne evoked a stepwise 2.5-6.3-fold stimulation of insulin secretion from the
BRIN-BD11 pancreatic B-cell line. This effect was abolished by 0.5 mM-diazoxide, and prior
exposure to extract did not affect subsequent stimulation of insulin secretion by 10 mM-L-alanine,
thereby negating a detrimental effect on cell viability. The effect of extract was potentiated by
16.7 mM-glucose and by 1 mM-3-isobutyl-1-methylxanthine. L-Alanine (10 mM) and a
depolarizing concentration of KCl (25 mM) did not augment the insulin-releasing activity of
lucerne. Activity of the extract was found to be heat stable and largely acetone insoluble, and was
enhanced by exposure to acid and alkali (0.1 M-HCl and NaOH) but decreased 25% with dialysis
to remove components with molecular mass < 2000 Da. Sequential extraction with solvents
revealed insulin-releasing activity in both methanol and water fractions indicating a cumulative
effect of more than one extract constituent. The results demonstrate the presence of
antihyperglycaemic, insulin-releasing and insulin-like activity in the traditional antidiabetic plant,
Medicago sativa.
PMID: 9301421 [PubMed - indexed for MEDLINE]
21: Ala J Med Sci. 1969 Oct;6(4):455-63.
Related Articles, Links
Biological effects of Gymnema sylvestre fractions. II. Electrophysiology--effect of gymnemic
acid on taste receptor response.
Yackzan KS.
PMID: 5363232 [PubMed - indexed for MEDLINE]
22: J Vet Med Sci. 1997 Apr;59(4):245-51.
Related Articles, Links
Suppression of glucose absorption by some fractions extracted from Gymnema sylvestre
leaves.
Shimizu K, Iino A, Nakajima J, Tanaka K, Nakajyo S, Urakawa N, Atsuchi M, Wada T,
Yamashita C.
Division of Veterinary Pharmacology, Nippon Veterinary and Animal Science University, Tokyo,
Japan.
Extracts containing gymnemic acids, which were extracted from the leaves of Gymnema sylvestre
(GS) as nine fractions, were evaluated for their effects on a high K(+)-induced contraction of
guinea-pig ileal longitudinal muscles, on glucose transport mediated by the difference of glucoseevoked transmural potential difference (delta PD) in the inverted intestine of guinea-pig and rat,
and on blood glucose in rat. Among nine fractions obtained by high performance liquid
chromatography from the extract, f-2 and f-4 strongly suppressed the high K(+)-induced
contraction of the ileal muscle, f-3 and f-5 did so moderately, and f-8 and f-9 did so weakly,
whereas the other fractions did not affect it. The degree of suppression of high K(+)-induced
contraction by f-2 at 74% was almost the same as that of f-4 at 67%, at concentrations of 0.1
mg/ml. The suppressed contraction by f-2 or f-4 was recovered by adding 5.5 mM pyruvate. The
delta PD increased by 5.5 mM glucose in the inverted intestines of guinea-pig and rat were equally
suppressed by 0.1 mg/ml of f-2 or f-4 to 40%. In a rat sucrose tolerance test, f-2 and f-4
suppressed the elevation of blood glucose level. Both f-2 and f-4 suppressed the contraction of
guinea-pig ileal longitudinal muscle, interfered with the increase in delta PD induced by glucose in
the inverted intestines of guinea-pig and rat, and inhibited the elevation of blood glucose level. In
conclusion, it is suggested that some of the extracts containing gymnemic acids from GS leaves
suppress the elevation of blood glucose level by inhibiting glucose uptake in the intestine.
PMID: 9152931 [PubMed - indexed for MEDLINE]
23: Ala J Med Sci. 1970 Jan;7(1):77-9.
Related Articles, Links
Biological effects of Gymnema sylvestre fractions. 3. Electrophysiology-in vitro gastric
membrane findings.
Yackzan KS.
PMID: 5428555 [PubMed - indexed for MEDLINE]
24: Ala J Med Sci. 1977 Apr;14(2):150-6.
Related Articles, Links
Sensory effects of Gymnema sylvestre: implications of Mass action and chemical kinetics.
Yackzan KS, Stoll PJ.
PMID: 855895 [PubMed - indexed for MEDLINE]
25: Physiol Behav. 1970 Dec;5(12):1379-84.
Related Articles, Links
Effects of Gymnema sylvestre on complex tastes elicited by amino acids and sucrose.
Meiselman HL, Halpern BP.
PMID: 5524525 [PubMed - indexed for MEDLINE]
26: Physiol Behav. 1970 Aug;5(8):945-8.
Related Articles, Links
Human judgments of Gymnema sylvestre and sucrose mixtures.
Meiselman HL, Halperin BP.
PMID: 5522511 [PubMed - indexed for MEDLINE]
J Vet Med Sci. 1997 Sep;59(9):753-7.
Related Articles, Links
Suppression of glucose absorption by extracts from the leaves of Gymnema inodorum.
Shimizu K, Ozeki M, Tanaka K, Itoh K, Nakajyo S, Urakawa N, Atsuchi M.
Division of Veterinary Pharmacology, Nippon Veterinary and Animal Science University, Tokyo,
Japan.
Gymnema sylvestre (GS) is one of the Asclepiad strains that grows in South-east Asia. Their
therapeutic effects for treating diabetes mellitus, rheumatic arthritis and gout have been well
known for a long time. However, the problem is that GS suppresses sweetness and tastes bitter.
For this study, we chose Gymnema inodorum (GI) instead of GS, since it has an advantage that it
does not suppress sweetness nor is it bitter in taste. In this paper, effects of glucose availability of
some saponin fractions (F-I to F-IV) extracted from GI leaves, which were obtained by highperformance liquid chromatography were studied on a high K(+)-induced contraction of guineapig intestinal smooth muscle, O2 consumption on guinea-pig ileum, glucose-evoked transmural
potential difference (delta PD) of guinea-pig everted intestine and blood glucose level in glucose
tolerance tests on rats. The extracts of GI leaves suppressed the intestinal smooth muscle
contraction, decreased the O2 consumption, inhibited the glucose evoked-transmural potential, and
prevented the blood glucose level. Our studies suggest that the component of GI inhibits the
increase in the blood glucose level by interfering with the intestinal glucose absorption process.
PMID: 9342697 [PubMed - indexed for MEDLINE]
2: J Smooth Muscle Res. 1996 Oct;32(5):219-28.
Related Articles, Links
[Inhibitory effects of glucose utilization by gymnema acids in the guinea-pig ileal
longitudinal muscle]
[Article in Japanese]
Shimizu K, Abe T, Nakajyo S, Urakawa N, Atsuchi M, Yamashita C.
Division of Veterinary Pharmacology, Nippon Veterinary and Animal Science University, Tokyo,
Japan.
Two substances identified as ((3 beta, 4 alpha, 16 beta, 21 beta, 22 alpha)-21-tigloxy-16, 22, 23,
28-tetrahydroxyolean-12-en-3-yl-beta D-glucopyranosiduronic acid) (GA1) and ((3 beta, 4 alpha,
16 beta, 21 beta, 22 alpha)-21-(2-methylbutyroxy)-16, 22, 23, 28-tetrahydroxyolean-12-en-3-ylbeta-D-glucopyranosiduronic acid) (GA2) identified among the gymnemic acids are triterpene
glycosides extracted from Gymnema sylvestre leaves. We examined the effects of GA1 or GA2 on
high K(+)-induced contraction in the guinea-pig longitudinal muscle. A sustained muscle
contraction induced by hyperosmotically added 65.4 mM KCI (H-65K+) was suppressed by GA1
or GA2 (7.7 x 10(-5) M). Simultaneous measurements of reduced pyridine nucleotide (PNred) or
oxidized flavin protein (FPox) by the fluorescence technique and of contractile force revealed that
GA1 and GA2 reduced the increase of PNred fluorescence and contractile force induced by H65K+, whereas FPox fluorescence induced by it further increased. Reduced muscle contraction
induced by GA1 or GA2 was restored by 5.5 mM pyruvate. Simultaneous measurements of
intracellular Ca2+ [Ca2+]1 level and contractile force indicated that [Ca2+]1 level, which
increased by H-65K+, hardly changed with GA1 and GA2. In summary, both GA1 and GA2,
which are among the gymnemic acids, suppressed high K(+)-induced contraction in the guinea-pig
ileal longitudinal muscle. The difference between these two gymnemic acids was not significant.
The inhibitory effect of GA1 and GA2 on smooth muscle were assumed to be a result of inhibiting
glucose uptake, which is an energy source of the muscle, whereas the inhibitory mechanisms were
probably not mediated by Ca2+.
PMID: 8985922 [PubMed - indexed for MEDLINE]
3: Jpn J Pharmacol. 2001 Jun;86(2):223-9.
Related Articles, Links
Structure-activity relationships of triterpenoid derivatives extracted from Gymnema
inodorum leaves on glucose absorption.
Shimizu K, Ozeki M, Iino A, Nakajyo S, Urakawa N, Atsuchi M.
Division of Veterinary Pharmacology, Nippon Veterinary and Animal Science University,
Musashino-shi, Tokyo, Japan.
The leaves of Gymnema inodorum (GI) have been known to be effective for some diseases
including diabetes mellitus, rheumatic arthritis and gout. The crude saponin mixtures extracted
from GI leaves inhibited glucose absorption in the isolated intestinal tract and suppressed the
increased blood glucose in rats. In this study, we examined the relationship between chemical
structure and pharmacological activity of the four components from GI leave extracts (GiA-1,
GiA-2, GiA-5 and GiA-7). These components were the derivatives of (3beta,4alpha,16beta)-
16,23,28-trihydroxyolean-12-en-3-yl-beta-D-glucopyranosiduroic acid. GiA-2, GiA-5 and GiA-7
that have suppressive effects on the high K+-induced contraction, an increase in deltaPD and the
increased blood glucose level in the glucose tolerance test have -H at the 21st position and CH2OH at 4beta of aglycon. On the other hand, GiA-1 that does not have any effects on the three
parameters mentioned above has -H at the 21st position and -CH3 at 4beta of aglycon. In
conclusion, it is suggested that the inhibitory effect of triterpenoids in Gymnema leaves on glucose
absorption from the intestinal tract relies on -CH2OH at 4beta.
PMID: 11459125 [PubMed - indexed for MEDLINE]
4: Chem Pharm Bull (Tokyo). 1997 Dec;45(12):2034-8.
Related Articles, Links
Medicinal foodstuffs. X. Structures of new triterpene glycosides, gymnemosides-c, -d, -e, and
-f, from the leaves of Gymnema sylvestre R. Br.: influence of gymnema glycosides on glucose
uptake in rat small intestinal fragments.
Yoshikawa M, Murakami T, Matsuda H.
Kyoto Pharmaceutical University, Japan.
Following the characterization of gymnemosides-a and -b, new triterpene glycosides,
gymnemosides-c, -d, -e, and -f, were isolated from the leaves of Gymnema (G.) sylvestre R. BR.
Their chemical structures were elucidated on the basis of chemical and physicochemical evidence
as follows: 21-O-benzoyl-28-O-acetylgymnemagenin 3-O-beta-D-glucopyranosiduronic acid
(gymnemoside-c), 23-O-[beta-D-xylopyranosyl (1-->6)-beta-D-glucopyranosyl (1-->6)-beta-Dglucopyranosyl] gymnestrogenin (gymnemoside-d), 23-O-[beta-D-xylopyranosyl (1-->6)-beta-Dglucopyranosyl (1-->6)-beta-D- glucopyranosyl]-28-O-[beta-D-glucopyranosyl (1-->6)-beta-Dglucopyranosyl] 23-hydroxylongispinogenin (gymnemoside-e), 23-O-[beta-D-xylopyranosyl (1->6)-beta-D-glucopyranosyl (1-->6)-beta-D-glucopyranosyl]-28-O-[beta-O-glucopyranosyl (1->6)-beta-D-glucopyranosyl] 3 beta,16 beta,23,28-tetrahydroxyolean-18-ene (gymnemoside-f). The
inhibitory effects of gymnemosides-c, -d, -e, and -f and principal triterpene glycosides from G.
sylvestre on glucose uptake in rat small intestinal fragments were examined, and gymnemic acids
II, III, and IV, gymnemasaponin V, and gymnemoside-f were found to exhibit the inhibitory
activity.
PMID: 9433774 [PubMed - indexed for MEDLINE]
5: Chem Pharm Bull (Tokyo). 1997 Oct;45(10):1671-6.
Related Articles, Links
Medicinal foodstuffs. IX. The inhibitors of glucose absorption from the leaves of Gymnema
sylvestre R. BR. (Asclepiadaceae): structures of gymnemosides a and b.
Yoshikawa M, Murakami T, Kadoya M, Li Y, Murakami N, Yamahara J, Matsuda H.
Kyoto Pharmaceutical University, Japan.
Although the glycosidic fraction from the dried leaves of Gymnema sylvestre R. BR., gymnemic
acid, was reported to be effective for diabetes, it showed little inhibitory activity on the increase of
serum glucose level in oral glucose-loaded rats. From the glycosidic fraction, six triterpene
glycosides, gymnemosides a, b, c, d, e, and f, were isolated together with nine known triterpene
glycosides. The structures of gymnemosides a and b were determined on the basis of chemical and
physicochemical evidence as 21-O-tigloyl-22-O-acetylgymnemagenin 3-O-beta-D-
glucopyranosiduronic acid and 16-O-acetyl-21-O-tigloylgymnemagenin 3-O-beta-Dglucopyranosiduronic acid, respectively. In addition, an acetyl group linked to the 16- or 22hydroxyl group in gymnemosides a and b was found to migrate easily to the primary 28-hydroxyl
group, while the acyl migration from the 28-position was rarely observed. The inhibitory activity
of each triterpene glycoside from gymnemic acid was examined to determine its impact on the
increase of serum glucose level in oral glucose-loaded rats. Gymnemoside b and gymnemic acids
III, V, and VII were found to exhibit a little inhibitory activity against glucose absorption, but the
principal constituents, gymnemic acid I and gymnemasaponin V, lacked this activity.
PMID: 9353896 [PubMed - indexed for MEDLINE]
6: J Asian Nat Prod Res. 2000;2(4):321-7.
Related Articles, Links
Antihyperglycemic effects of gymnemic acid IV, a compound derived from Gymnema
sylvestre leaves in streptozotocin-diabetic mice.
Sugihara Y, Nojima H, Matsuda H, Murakami T, Yoshikawa M, Kimura I.
Department of Chemical Pharmacology, Toyama Medical and Pharmaceutical University,
Sugitani, Japan.
We investigated the antihyperglycemic action of a crude saponin fraction and five triterpene
glycosides (gymnemic acids I-IV and gymnemasaponin V) derived from the methanol extract of
leaves of Gymnema sylvestre R. BR. (Asclepiadaceae) in streptozotocin (STZ)-diabetic mice. The
saponin fraction (60mg/kg) reduced blood glucose levels 2 4h after the intraperitoneal
administration. Gymnemic acid IV, not the other 4 glycosides at doses of 3.4-13.4mg/kg reduced
the blood glucose levels by 13.5-60.0% 6h after the administration comparable to the potency of
glibenclamide, and did not change the blood glucose levels of normal mice. Gymnemic acid IV at
13.4 mg/kg increased plasma insulin levels in STZ-diabetic mice. Gymnemic acid IV (1 mg/mL)
did not inhibit alpha-glycosidase activity in the brush border membrane vesicles of normal rat
small intestines. These results indicate that insulin-releasing action of gymnemic acid IV may
contribute to the antihyperglycemic effect by the leaves of G. sylvestre. Gymnemic acid IV may
be an anti-obese and antihyperglycemic pro-drug.
PMID: 11249615 [PubMed - indexed for MEDLINE]
7: J Ethnopharmacol. 1999 Dec 15;68(1-3):307-14.
Related Articles, Links
Improving effects of the extracts from Eugenia uniflora on hyperglycemia and
hypertriglyceridemia in mice.
Arai I, Amagaya S, Komatsu Y, Okada M, Hayashi T, Kasai M, Arisawa M, Momose Y.
Central Research Laboratories, Tsumura & Company, Ibaraki, Japan.
[email protected]
EtOH (70%) extracts from the leaves of Eugenia uniflora were separated into six fractions with
different polarity and molecular size, i.e. NP-1-NP-6. In an oral glucose tolerance test, NP-1 and 4
inhibited the increase in plasma glucose level. However, in an intraperitoneal glucose tolerance
test, such an inhibitory effect was not seen. Thus, the effects of NP-1 and 4 were apparently due to
the inhibition of glucose absorption from the intestine. In a sucrose tolerance test, all fractions
inhibited the increase in plasma glucose level. In an oral corn oil tolerance test, NP-3 and 4
showed an inhibitory effect on the increase in plasma triglycerides level. On the other hand, NP-3,
4, 5 and 6 inhibited maltase and sucrase activities and all fractions except for NP-1 showed an
inhibitory effect on lipase activity dose-dependently. The inhibition of the increase in plasma
glucose level by NP-3, 4, 5 and 6 in the oral sucrose tolerance test and the inhibition of the
increase in plasma triglycerides by NP-3 and 4 in the oral corn oil tolerance test were apparently
due to the inhibition of the decomposition of carbohydrates and fats in the intestine, respectively.
PMID: 10624893 [PubMed - indexed for MEDLINE]
8: J Nutr. 1999 Jun;129(6):1214-22.
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Fecal steroid excretion is increased in rats by oral administration of gymnemic acids
contained in Gymnema sylvestre leaves.
Nakamura Y, Tsumura Y, Tonogai Y, Shibata T.
Division of Food Chemistry, National Institute of Health Sciences, Osaka Branch, 1-1-43,
Hoenzaka, Chuo-ku, Osaka, 540-0006, Japan.
Gymnemic acids are the saponins with a triterpenoid structure contained in Gymnema sylvestre
leaves and have the hypoglycemic effects. In spite of the cholesterol-binding properties of
saponins, the effect of gymnemic acids on cholesterol metabolism has not been elucidated to date.
We investigated the effects of gymnemic acids on fecal steroid excretion in rats. Three kinds of
extracts from Gymnema sylvestre leaves, extract (GSE), acid precipitate (GSA) and column
fractionate (GSF), of which the gymnemagenin (an aglycone of gymnemic acids) concentrations
are 58.87, 161.6, and 363.3 mg/g respectively, were used for the experiments. These were
administered to rats orally at the dose of 0.05-1.0 g/kg for 22 d. Rats were given free access to
water and nonpurified diet without cholesterol, and the differences in fecal excretion of steroids
and gymnemic acids were investigated. Although there were no significant effects of GSE, GSA
and GSF decreased body weight gain and food intakes in a dose-dependent manner (P < 0.01).
GSF (1.0 g/kg) significantly increased fecal excretion of neutral steroids and bile acids in a dosedependent manner (P < 0.05), especially those of cholesterol and cholic acid (CA)-derived bile
acids. The increases in fecal steroid excretion of cholesterol, total neutral steroids, total bile acids
and CA-related bile acids were acute and significantly correlated with fecal gymnemagenin levels
(r2 = 0.2316-0.9861, P < 0. 05). These results demonstrated for the first time that a high dose of
gymnemic acids increases fecal cholesterol and CA-derived bile acid excretion. Further studies are
needed to clarify the effect of gymnemic acids on cholesterol metabolism.
PMID: 10356090 [PubMed - indexed for MEDLINE]
9: Methods Find Exp Clin Pharmacol. 1997 Oct;19(8):515-20.
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Triterpenoid compounds from Araujia sericifera B. Effects on the isolated guinea pig ileum.
Lopez de Medrano-Villar MJ, Bello R, Esplugues J, Primo-Yufera E, Primo-Millo J.
Departamento de Biotecnologia, Universidad Politecnica de Valencia, Spain.
Different fractions from the methanol insoluble extract of Araujia sericifera were obtained by
chromatography and evaluated for their antihistaminic effects on guinea pig ileum in vitro. In
order to determine the compounds responsible for the pharmacological effects observed,
separation of the components from the active fraction was performed using HPLC.
PMID: 9442473 [PubMed - indexed for MEDLINE]
10: Pharmazie. 2003 Jun;58(6):413-5.
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Effects of Inula racemosa root and Gymnema sylvestre leaf extracts in the regulation of
corticosteroid induced diabetes mellitus: involvement of thyroid hormones.
Gholap S, Kar A.
Thyroid Research Unit, School of Life Sciences, D. A. University, Khandwa Road, Indore, India.
The efficacy of Inula racemosa (root) and Gymnema sylvestre (leaf) extracts either alone or in
combination was evaluated in the amelioration of corticosteroid-induced hyperglycaemia in mice.
Simultaneously thyroid hormone levels were estimated by radio-immunoassay (RIA) in order to
ascertain whether the effects are mediated through thyroid hormones or not. While the
corticosteroid (dexamethasone) administration increased the serum glucose concentration, it
decreased serum concentrations of the thyroid hormones, thyroxine (T4) and triiodothyronine (T3).
Administration of the two plant extracts either alone or in combination decreased the serum
glucose concentration in dexamethasone induced hyperglycaemic animals. However, the
administration of Inula racemosa and Gymnema sylvestre extracts in combination proved to be
more effective than the individual extracts. These effects were comparable to a standard
corticosteroid-inhibiting drug, ketoconazole. As no marked changes in thyroid hormone
concentrations were observed by the administration of any of the plant extracts in dexamethasone
treated animals, it is further suggested that these plant extracts may not prove to be effective in
thyroid hormone mediated type II diabetes, but for steroid induced diabetes.
PMID: 12857006 [PubMed - indexed for MEDLINE]
11: Biosci Biotechnol Biochem. 1998 Jun;62(6):1225-7.
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Suppression by water extracts of Sophora plants of sucrose-induced hyperglycemia in rats
and inhibition of intestinal disaccharidases in vitro.
Shi HC, Huang QY, Yamaji R, Inui H, Fujita T, Miyatake K, Nakano Y, Tada T, Nishimura
K.
Department of Applied Biological Chemistry, Osaka Prefecture University, Japan.
Partially purified hot-water extracts of the roots of plants of the Sophora family suppressed the
increase in blood glucose concentration of rats in the oral sugar tolerance test. The extracts also
inhibited rat intestinal sucrase and maltase. The most potent sample was about 15 times more
active than catechin, a positive control, in these experiments.
PMID: 9692207 [PubMed - indexed for MEDLINE]
12: J Ethnopharmacol. 2000 Sep;72(1-2):129-33.
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Hypoglycemic effect of Equisetum myriochaetum aerial parts on streptozotocin diabetic rats.
Andrade Cetto A, Wiedenfeld H, Revilla MC, Sergio IA.
Biological Department, Science School, National University of Mexico UNAM, DF., 04510
Mexico, Mexico.
The hypoglycemic effect of water as well as butanolic extracts prepared from aerial parts of
Equisetum myriochaetum (Equisetaceae) was examined in streptozotocin induced diabetic rats. A
single oral administration of the water extract (WE) at doses of 7 and 13 mg/kg and of the butanol
extract (BE) at doses of 8 and 16 mg/kg significantly (P<0.001) lowered the plasma glucose levels
in diabetic rats after three hours of the administration. As a reference drug glibenclamide was used
and showed, at a dose of 3 mg/kg, similar hypoglycemic effect like the tested extracts. Three
kaempferol glucosides and one caffeoyl glucoside were isolated from the drug and were shown to
be the main constituents in both extracts.
PMID: 10967463 [PubMed - indexed for MEDLINE]
13: Biol Pharm Bull. 2001 Jun;24(6):713-7.
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Effect of administration with the extract of Gymnema sylvestre R. Br leaves on lipid
metabolism in rats.
Shigematsu N, Asano R, Shimosaka M, Okazaki M.
Biosci. Textile Technol., Shinshu University, Ueda, Nagano, Japan. [email protected]
Extract of Gymnema sylvestre R. Br leaves (GE) was orally administered once a day to rats fed a
high fat diet or normal fat diet for 3 weeks to investigate its influence on lipid metabolism. As a
result, GE did not influence body weight gain or feed intake in both diet groups during the
experimental period. The apparent fat digestibility was significantly decreased by GE in both diet
groups for the last 2 weeks of the experimental period, though not the apparent protein
digestibility. In addition, the excretion of neutral sterols and acid steroids into feces was increased
by GE in both diet groups. Furthermore, GE decreased the total cholesterol and triglyceride levels
in serum. On the other hand, blood lecithin-cholesterol acyltransferase (LCAT) activity was
increased by GE. Moreover, it was suggested that GE influenced cecal fermentation and that
propionic acid and acetic acid contents in cecum were significantly increased by GE.
Consequently, it was suggested that GE improved serum cholesterol and triglyceride levels
through influence over a wide range of lipid metabolism in rats.
PMID: 11411567 [PubMed - indexed for MEDLINE]
14: J Pharm Pharmacol. 1999 Nov;51(11):1321-4.
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Evaluation of the anti-diabetic property of Morinda lucida leaves in streptozotocin-diabetic
rats.
Olajide OA, Awe SO, Makinde JM, Morebise O.
Department of Pharmacology, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife,
Nigeria. [email protected]
The hypoglycaemic and anti-hyperglycaemic activities of a methanol extract of Morinda lucida
Benth. (Rubiaceae) leaves were studied in normal and streptozotocin-diabetic rats. In normal rats,
the extract demonstrated a significant (P < 0.05) and dose-dependent hypoglycaemic activity
within 4 h after oral administration. The plasma glucose level of 400 mg kg(-1) of the extract at 4
h was 42.5 +/- 0.4 mg/100 mL (control 67.4 +/- 1.2 mg/100 mL). After 12 h, the plasma glucose
level of rats administered 50, 100, 200 or 400 mg kg(-1) extract fell to 51.9 +/- 1.2, 47.3 +/- 0.8,
43.1 +/- 0.4 and 40.0 +/- 0.5 mg/100 mL, respectively. In hyperglycaemic rats, the extract
produced a significant (P < 0.05) anti-diabetic effect from day 3 after oral administration, with 400
mg kg(-1) extract-treated animals having a plasma glucose level of 248.7 +/- 5.3 mg/100 mL
compared with glibenclamide (10 mg kg(-1))-treated animals with a plasma glucose level of 251.5
+/- 5.8 mg/100 mL. These results suggest that the leaves of Morinda lucida have a strong glucose
lowering property when administered to streptozotocin-treated rats.
PMID: 10632091 [PubMed - indexed for MEDLINE]
15: Gen Pharmacol. 1998 Sep;31(3):495-6.
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Possible mechanism of antihyperglycemic effect of Gymnema sylvestre leaf extract, part I.
Chattopadhyay RR.
Indian Statistical Institute, Calcutta.
1. Effect of water soluble fraction of alcoholic extract of G. sylvestre leaves on glycogen content
by isolated rat hemidiaphragm was studied in normal and glucose fed hyperglycemic rats. 2. The
leaf extract by itself failed to alter the hepatic glycogen content in normal rats. 3. In glucose fed
rats, the leaf extract lowered the glycogen content of the tissue significantly (P<0.05) and this was
further lowered when both exogenous insulin and leaf extract was administered. 4. The results are
discussed.
PMID: 9703226 [PubMed - indexed for MEDLINE]
16: Biol Pharm Bull. 2001 Jun;24(6):643-9.
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Effect of long term-administration with Gymnema sylvestre R. BR on plasma and liver lipid
in rats.
Shigematsu N, Asano R, Shimosaka M, Okazaki M.
Biosci. Textile Technol., Shinshu University, Ueda, Nagano, Japan. [email protected]
Extract of Gymnema sylvestre leaves was administered to rats receiving either a high fat diet or
normal fat diet for 10 weeks to investigate its influence on plasma and liver lipids and on visceral
fat accumulation. In addition, its effect was compared with those of chitosan and the influence of
combined use of these two substances was also evaluated. Within the high fat diet groups, the
extract suppressed body weight gain and accumulation of liver lipids to the same extent as
chitosan and the combined use. In addition, intraperitoneal fat and fat drop vacuoles on the
epithelium of renal tubules, noted in the high fat diet group, were scattered by administration of
the extract with the same results as for chitosan and combined use. Within the normal fat diet
groups, plasma triglyceride levels decreased by administration of the extract, with similar results
as chitosan and combined use. Concerning plasma total cholesterol, there was no decreasing
effects with the extract, as found with chitosan and combined use. However, the effect of chitosan
on plasma total cholesterol tended to be enhanced when used in combination with the extract. In
addition, long-term administration of the extract did not show any influence on hematological and
blood chemical parameters.
PMID: 11411552 [PubMed - indexed for MEDLINE]
17: J Ethnopharmacol. 1986 Nov;18(2):143-6.
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Effect of feeding Gymnema sylvestre leaves on blood glucose in beryllium nitrate treated
rats.
Prakash AO, Mathur S, Mathur R.
The feeding of powdered leaves of Gymnema sylvestre in the diet of rats for 10 days prior and 15
days after i.v. beryllium nitrate significantly protected the animals from the full fall of blood
glucose seen in rats receiving beryllium nitrate alone. The feeding of the leaves for 25 days to
normal rats did not alter blood glucose significantly. The leaves may contain a principle that could
be useful as a prophylactic against beryllium toxicity.
PMID: 3560992 [PubMed - indexed for MEDLINE]
18: Helv Chim Acta. 1968;51(6):1235-42.
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[Gymnestrogenin, a new pentahydroxytriterpene from the leaves of Gymnema sylvestre
R.Br.]
[Article in German]
Stocklin W.
PMID: 5680734 [PubMed - indexed for MEDLINE]
19: Comp Biochem Physiol. 1968 Jun;25(3):1091-7.
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Failure of Gymnema extract to inhibit the sugar receptors of two invertebrates.
Larimer JL, Oakley B.
PMID: 5758866 [PubMed - indexed for MEDLINE]
20: Life Sci. 1969 May 1;8(9):537-43.
Antisweet activity of gymnemic acid A1 and its derivatives.
Kurihara Y.
Related Articles, Links
PMID: 5791706 [PubMed - indexed for MEDLINE]
1: Isr J Med Sci. 1985 Jun;21(6):540-2.
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Hypoglycemic and life-prolonging properties of Gymnema sylvestre leaf extract in diabetic
rats.
Srivastava Y, Nigam SK, Bhatt HV, Verma Y, Prem AS.
PMID: 4019152 [PubMed - indexed for MEDLINE]
2: J Ethnopharmacol. 1990 Oct;30(3):281-94.
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Use of Gymnema sylvestre leaf extract in the control of blood glucose in insulin-dependent
diabetes mellitus.
Shanmugasundaram ER, Rajeswari G, Baskaran K, Rajesh Kumar BR, Radha
Shanmugasundaram K, Kizar Ahmath B.
Department of Biochemistry, University of Madras, India.
GS4, a water-soluble extract of the leaves of Gymnema sylvestre, was administered (400 mg/day)
to 27 patients with insulin-dependent diabetes mellitus (IDDM) on insulin therapy. Insulin
requirements came down together with fasting blood glucose and glycosylated haemoglobin
(HbA1c) and glycosylated plasma protein levels. While serum lipids returned to near normal
levels with GS4 therapy, glycosylated haemoglobin and glycosylated plasma protein levels
remained higher than controls. IDDM patients on insulin therapy only showed no significant
reduction in serum lipids, HbA1c or glycosylated plasma proteins when followed up after 10-12
months. GS4 therapy appears to enhance endogenous insulin, possibly by
regeneration/revitalisation of the residual beta cells in insulin-dependent diabetes mellitus.
Publication Types:

Clinical Trial
PMID: 2259216 [PubMed - indexed for MEDLINE]
3: Planta Med. 1996 Oct;62(5):440-3.
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Hypoglycemic effect of the rhizomes of Polygala senega in normal and diabetic mice and its
main component, the triterpenoid glycoside senegin-II.
Kako M, Miura T, Nishiyama Y, Ichimaru M, Moriyasu M, Kato A.
Suzuka University of Medical Science and Technology, Mie, Japan.
The hypoglycemic effect of the rhizomes of Polygala senega L. var. latifolia Torrey et Gray
(Polygalaceae) was investigated in normal and KK-Ay mice, one of the model animals of noninsulin dependent diabetes mellitus (NIDDM). The n-butanol extract of senega rhizomes (SN) (5
mg/kg) reduced the blood glucose of normal mice from 191 +/- 3 to 120 +/- 3 mg/dl 4 hours after
intraperitoneal administration (P < 0.001), and also showed a significant decrease in the glucose
level of KK-Ay mice from 469 +/- 38 to 244 +/- 14 mg/dl under similar conditions (P < 0.001).
But streptozotocin-induced diabetic mice did not experience a change in the blood glucose after
administration of SN. We propose that the hypoglycemic effect of SN occurs without altering the
insulin concentration. Moreover, SN needs the presence of insulin in order to act. In addition, one
of the active components of the hypoglycemic effect was identified as a triterpenoid glycoside,
senegin-II.
PMID: 8923811 [PubMed - indexed for MEDLINE]
4: Planta Med. 1994 Jun;60(3):244-7.
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Hypoglycemic and antihyperglycemic effects of Zizyphus spina-christi in rats.
Glombitza KW, Mahran GH, Mirhom YW, Michel KG, Motawi TK.
Institute of Pharmaceutical Biology, Bonn University, Federal Republic of Germany.
Zizyphus is one of the plants commonly used in Egyptian folk medicine for the treatment of
different diseases. The present study aims to investigate the effect of the butanol extract of
Zizyphus spina-christi leaves as well as christinin-A, its principle saponin glycoside, in normal
and streptozotocin-diabetic rats. In normal rats, treatment in both cases for one and four weeks
produced insignificant changes in all studied parameters. However, in diabetic rats, both
treatments significantly reduced serum glucose level, liver phosphorylase and glucose-6phosphatase (G-6-pase) activities, and significantly increased serum pyruvate level and liver
glycogen content after 4 weeks treatment. There was also marked improvement in glucose
utilization in diabetic rats in both cases. Serum insulin and pancreatic cAMP levels showed
significant increases in diabetic rats treated for a period of 4 weeks with the butanol extract.
PMID: 8073092 [PubMed - indexed for MEDLINE]
5: Fitoterapia. 2002 Apr;73(2):156-9.
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Hypoglycemic activity of Abutilon indicum leaf extracts in rats.
Seetharam YN, Chalageri G, Setty SR, Bheemachar.
Biosystematics and Medicinal Plant Laboratory, Department of Botany, Gulbarga University, 585
106, Gulbarga, India.
Alcohol and water extracts of Abutilon indicum leaves (400 mg/kg, p.o.) showed significant
hypoglycemic effect in normal rats 4 h after administration (23.10% and 26.95%, respectively).
PMID: 11978431 [PubMed - indexed for MEDLINE]
6: J Ethnopharmacol. 1988 Jan;22(1):81-90.
Effect of Cassia alata leaf extract on hyperglycemic rats.
Palanichamy S, Nagarajan S, Devasagayam M.
Related Articles, Links
Department of Chemistry, Bharathidasan University, Tiruchirapalli, India.
The oral effectiveness of Cassia alata leaf extract on streptozotocin-induced hyperglycemia in rats
has been studied and the results compared with glybenclamide. While the extract has no effect on
glucose levels in normoglycemic animals, it reduced the blood sugar value in streptozotocininduced hyperglycemic animals.
PMID: 3352288 [PubMed - indexed for MEDLINE]
7: J Ethnopharmacol. 1998 Feb;60(1):27-32.
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Hypoglycemic effect of the water extract of Piper sarmentosum in rats.
Peungvicha P, Thirawarapan SS, Temsiririrkkul R, Watanabe H, Kumar Prasain J, Kadota
S.
Department of Physiology, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
The hypoglycemic effect of the water extract of the whole plant of Piper sarmentosum Roxb.
(Piperaceae, Thai name: Chaplu) was examined in normal and streptozotocin-diabetic rats. In an
oral glucose tolerance test, a single oral administration of the water extract at doses of 0.125 and
0.25 g/kg significantly lowered the plasma glucose level in the normal rats. A reference drug,
glibenclamide, at a dose of 5 mg/kg (per os, p.o.) also showed a significant hypoglycemic effect in
the normal rats. In contrast, a single oral administration of the water extract at these doses and
glibenclamide did not significantly lower the plasma glucose level in the diabetic rats. However,
the repeated oral administration of the water extract at a dose of 0.125 g/kg for 7 days produced a
significant hypoglycemic effect in the diabetic rats. Glibenclamide (5 mg/kg, p.o.) also caused
significant hypoglycemia in the diabetic rats. These results demonstrated that the water extract of
whole plant of Piper sarmentosum has a hypoglycemic effect in rats.
PMID: 9533429 [PubMed - indexed for MEDLINE]
8: Biomed Environ Sci. 1999 Sep;12(3):222-6.
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A preliminary investigation of the possible hypoglycemic activity of Hibiscus rosa-sinensis.
Sachdewa A, Khemani LD.
Department of Chemistry, Faculty of Science, Dayalbagh Educational Institute, Agra, India.
The hypoglycemic activity of an ethanol extract of Hibiscus rosa-sinensis was studied in glucose
located rats. After a single dose of the extract, a slight but insignificant hypoglycemic effect was
observed at 30 and 90 min. At 120 min it was mild but significant. After repeated administration
of the extract (once a day for seven consecutive days) a statistically significant (P < 0.001)
reduction in blood glucose levels was observed at 30, 90 and 120 min after glucose loading. The
average hypoglycemic activity, after repeated administration of 250 mg kg-1 leaf extract was 81%,
under similar conditions average activity of tolbutamide was 96%. At 250 mg.kg-1 the efficacy of
the extract was found to be 84% of tolbutamide (100 mg.kg-1). Repeated treatment of animals
either with tolbutamide a sulphonylurea or H. rosa-sinensis caused a 2-3-fold improvement in
glucose tolerance as compared to those receiving only once. These data suggest that the leaf
extract acts like tolbutamide and the mechanism of action may be a stimulation of pancreatic beta
cells to produce more insulin or an increase of the glycogen deposition in liver. It appears that the
active principle in the tested extract has the sulphonylurea skeleton in which-SO2-NH-CO-group
and the substituents (S1 and S2) may be the possible active sites responsible for its hypoglycemic
activity.
PMID: 10674186 [PubMed - indexed for MEDLINE]
9: J Med Food. 2003 Spring;6(1):43-9.
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Effect of Gymnema montanum on blood glucose, plasma insulin, and carbohydrate
metabolic enzymes in alloxan-induced diabetic rats.
Ananthan R, Latha M, Pari L, Ramkumar KM, Baskar CG, Bai VN.
Department of Botany, Bharathiar University, Coimbatore-641 046, Tamil Nadu, India.
The effects of Gymnema montanum, an endangered plant used in the ancient period of India, on
blood glucose, plasma insulin, and carbohydrate metabolic enzymes were studied in alloxan
diabetic rats. Administration of alcoholic extract of G. montanum leaves (50, 100, 200 mg/kg
body weight) to alloxan diabetic rats for 3 weeks reduced the blood glucose level. Administration
of G. montanum leaf extract (GLEt) at 200 mg/kg body weight significantly decreased the blood
glucose levels and significantly increased the plasma insulin levels. This clearly shows the
antidiabetic efficacy of GLEt, which was better than that of glibenclamide.
PMID: 12804019 [PubMed - indexed for MEDLINE]
10: J Ethnopharmacol. 1983 Mar;7(2):205-34.
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Enzyme changes and glucose utilisation in diabetic rabbits: the effect of Gymnema sylvestre,
R.Br.
Shanmugasundaram KR, Panneerselvam C, Samudram P, Shanmugasundaram ER.
The administration of the dried leaf powder of Gymnema sylvestre regulates the blood sugar levels
in alloxan diabetic rabbits. G. sylvestre therapy not only produced blood glucose homeostasis but
also increased the activities of the enzymes affording the utilisation of glucose by insulin
dependent pathways: it controlled phosphorylase levels, gluconeogenic enzymes and sorbitol
dehydrogenase. The uptake and incorporation of [14C] glucose into the glycogen and protein are
increased in the liver, kidney and muscle in G. sylvestre administered diabetic animals when
compared to the untreated diabetic animals. Pathological changes initiated in the liver during the
hyperglycemic phase are reversed by controlling hyperglycemia by G. sylvestre. G. sylvestre, a
herb used for the control of diabetes mellitus in several parts of India, appears to correct the
metabolic derangements in diabetic rabbit liver, kidney and muscle.
PMID: 6865451 [PubMed - indexed for MEDLINE]
11: J Ethnopharmacol. 2001 Feb;74(2):125-32.
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Hypoglycemic effect of the water extract of Smallantus sonchifolius (yacon) leaves in normal
and diabetic rats.
Aybar MJ, Sanchez Riera AN, Grau A, Sanchez SS.
Departamento de Biologia del Desarrollo, INSIBIO/CONICET, Universidad Nacional de
Tucuman (UNT), Chacabuco 461, 4000-San Miguel de Tucuman, Tucuman, Argentina
The hypoglycemic effect of the water extract of the leaves of Smallantus sonchifolius (yacon) was
examined in normal, transiently hyperglycemic and streptozotocin (STZ)-induced diabetic rats.
Ten-percent yacon decoction produced a significant decrease in plasma glucose levels in normal
rats when administered by intraperitoneal injection or gastric tube. In a glucose tolerance test, a
single administration of 10% yacon decoction lowered the plasma glucose levels in normal rats. In
contrast, a single oral or intraperitoneal administration of yacon decoction produced no effect on
the plasma glucose levels of STZ-induced diabetic rats. However, the administration of 2% yacon
tea ad libitum instead of water for 30 days produced a significant hypoglycemic effect on STZinduced diabetic rats. After 30 days of tea administration, diabetic rats showed improved body
(plasma glucose, plasma insulin levels, body weight) and renal parameters (kidney weight, kidney
to body weight ratio, creatinine clearance, urinary albumin excretion) in comparison with the
diabetic controls. Our results suggest that yacon water extract produces an increase in plasma
insulin concentration.
PMID: 11167030 [PubMed - indexed for MEDLINE]
12: J Ethnopharmacol. 2002 May;80(2-3):203-6.
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Effect of Cassia auriculata Linn. on serum glucose level, glucose utilization by isolated rat
hemidiaphragm.
Sabu MC, Subburaju T.
Amala Cancer Research Center, Amala Nagar, Thrissur 680 553, Kerala, India.
[email protected]
An aqueous leaf extract of Cassia auriculata (C. auriculata) was found to lower the serum glucose
level in normal rats. Maximum reduction in serum glucose level was observed after 4 h at a dose
levels of 100, 200, 400 mg/kg body weight of the extract. In normal rats the serum glucose level
reduction at 4th h was 23% by 100 mg/kg body weight and 31% by 200 mg/kg body weight. In
alloxan-induced diabetic rats, chronic administration of the extract significantly reduced the serum
glucose level from third day to till the end of the experiment. The extract was also found to inhibit
the body weight reduction induced by alloxan administration. Glucose uptake and glycogen
deposition studies suggest that C. auriculata leaf extract probably has no direct insulin like effect
which can enhance the peripheral utilization of glucose.
PMID: 12007712 [PubMed - indexed for MEDLINE]
13: Biol Pharm Bull. 1996 Mar;19(3):364-6.
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Hypoglycemic effect of water extract of the root of Pandanus odorus RIDL.
Peungvicha P, Thirawarapan SS, Watanabe H.
Department of Physiology, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
Hypoglycemic effect of water extract of the root of Pandanus odorus RIDL. (Thai name: Toeihom, Pandanaceae) was examined in normal and streptozotocin-diabetic rats. In the hypoglycemic
test without glucose load, an administration of the extract at doses of 0.125-0.5g/kg p.o. did not
affect significantly the plasma glucose level in normal rats, whereas the extract significantly
lowered the plasma glucose level at a dose of 0.5g/kg p.o. in diabetic rats. In oral glucose
tolerance test, an administration of the extract at a dose of 0.5g/kg p.o. significantly lowered the
plasma glucose level in normal rats. The extract at doses of 0.5 and 1.0g/kg p.o. also significantly
lowered the plasma glucose level in diabetic rats. A reference drug, glibenclamide at a dose of 5
mg/kg p.o. showed a significant hypoglycemic effect in both normal and diabetic rats. Repeated
administration of the extract at doses of 0.25 and 0.5 g/kg p.o. for 7d produced a significant
hypoglycemic effect in diabetic rats. Glibenclamide (5 mg/kg p.o.) also caused a significant
hypoglycemia in the diabetic rats. LD50 (95% confidence limit) after intraperitoneal injection was
1.87 (1.26-2.76)g/kg in male and female rats and 1.62 (1.18-2.24)g/kg in male and female mice,
respectively. The LD50 after oral administration was over 8 g/kg in both sexes of rat and mice.
PMID: 8924901 [PubMed - indexed for MEDLINE]
14: Planta Med. 1995 Aug;61(4):358-60.
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Characterization of the hypoglycemic effects of Trigonella foenum graecum seed.
Ali L, Azad Khan AK, Hassan Z, Mosihuzzaman M, Nahar N, Nasreen T, Nur-e-Alam M,
Rokeya B.
The whole powder of Trigonella foenum graecum seeds and its extracts were tested for their
hypoglycemic effect on normal and diabetic model rats. The powder, its methanol extract, and the
residue remaining after methanol extraction had significant hypoglycemic effects when fed
simultaneously with glucose. The water extract of the methanol extractive-free residue of the seed
powder showed significant hypoglycemic activity at different prandial states. The Soluble Dietary
Fibre (SDF) fraction showed no effect on the fasting blood glucose levels of nondiabetic or
NIDDM model rats. However, when fed simultaneously with glucose, it showed a significant
hypoglycemic effect (p < 0.05) in NIDDM model rats. Chemical analysis showed that the major
constituent of the SDF is a galactomannan. The results confirm the involvement of SDF in the
hypoglycemic effect of T. foenum graecum seeds. However, compound(s) other than SDF is (are)
also involved in the hypoglycemic activity.
Publication Types:

Letter
PMID: 7480183 [PubMed - indexed for MEDLINE]
15: Acta Pharmacol Sin. 2003 Jan;24(1):50-4.
Hypoglycemic activity of ginseng glycopeptide.
Related Articles, Links
Wang BX, Zhou QL, Yang M, Wang Y, Cui ZY, Liu YQ, Ikejima T.
Jilin Institute of Natural Medicine, Jilin University, Changchun 130021, China.
[email protected]
AIM: To study the hypoglycemic activity of ginseng glycopeptide (GGP). METHODS: Normal
mice or rabbits and alloxan or streptozotocin-induced hyperglycemic rats or mice were used in the
study. Blood glucose and liver glycogen levels of the experimental animals during the trial period
were analyzed by spectrophotometry with O-toluidine and iodine reagents, respectively.
RESULTS: Significant decreases in blood glucose and liver glycogen levels were induced in a
dose-dependent manner after administration of GGP 50, 100, or 200 mg/kg injected ip or sc to
normal mice and injected im 30 or 60 mg/kg to normal rabbits. The hypoglycemic activity of GGP
lasted for about 16 h, and were examined in both normal animals and hyperglycemic animals.
CONCLUSION: GGP injection induced the pronounced decreases in blood glucose and liver
glycogen levels in both normal and hyperglycemic animals.
PMID: 12511229 [PubMed - indexed for MEDLINE]
16: Phytother Res. 2001 Mar;15(2):157-61.
Related Articles, Links
Effect of Aloe vera leaves on blood glucose level in type I and type II diabetic rat models.
Okyar A, Can A, Akev N, Baktir G, Sutlupinar N.
Department of Pharmacology, Faculty of Pharmacy, University of Istanbul, 34452 Universite,
Istanbul, Turkey.
Aloe vera (L.) Burm. fil. (= A. barbadensis Miller) (Liliaceae) is native to North Africa and also
cultivated in Turkey. Aloes have long been used all over the world for their various medicinal
properties. In the past 15 years, there have been controversial reports on the hypoglycaemic
activity of Aloe species, probably due to differences in the parts of the plant used or to the model
of diabetes chosen. In this study, separate experiments on three main groups of rats, namely, nondiabetic (ND), type I (IDDM) and type II (NIDDM) diabetic rats were carried out. A. vera leaf
pulp and gel extracts were ineffective on lowering the blood sugar level of ND rats. A. vera leaf
pulp extract showed hypoglycaemic activity on IDDM and NIDDM rats, the effectiveness being
enhanced for type II diabetes in comparison with glibenclamide. On the contrary, A. vera leaf gel
extract showed hyperglycaemic activity on NIDDM rats. It may therefore be concluded that the
pulps of Aloe vera leaves devoid of the gel could be useful in the treatment of non-insulin
dependent diabetes mellitus Copyright 2001 John Wiley & Sons, Ltd.
PMID: 11268118 [PubMed - indexed for MEDLINE]
17: J Ethnopharmacol. 2001 Aug;76(3):269-77.
Related Articles, Links
Effect of an antidiabetic extract of Catharanthus roseus on enzymic activities in
streptozotocin induced diabetic rats.
Singh SN, Vats P, Suri S, Shyam R, Kumria MM, Ranganathan S, Sridharan K.
Defence Institute of Physiology and Allied Sciences, Lucknow Road, Timarpur, Delhi 110054,
India. [email protected]
Hypoglycemic activity was detected in dichloromethane:methanol extract (1:1) of leaves and
twigs of Catharanthus roseus (family Apocynaceae), a traditionally used medicinal plant, using
streptozotocin (STZ) induced diabetic rat model. Extract at dose 500 mg/kg given orally for 7 and
15 days showed 48.6 and 57.6% hypoglycemic activity, respectively. Prior treatment at the same
dose for 30 days provided complete protection against STZ challenge (75 mg/kg/i.p.x1). Enzymic
activities of glycogen synthase, glucose 6-phosphate-dehydrogenase, succinate dehydrogenase and
malate dehydrogenase were decreased in liver of diabetic animals in comparison to normal and
were significantly improved after treatment with extract at dose 500 mg/kg p.o. for 7 days. Results
indicate increased metabolization of glucose in treated rats. Increased levels of lipid peroxidation
measured as 2-thiobarbituric acid reactive substances (TBARS) indicative of oxidative stress in
diabetic rats were also normalized by treatment with the extract.
PMID: 11448549 [PubMed - indexed for MEDLINE]
18: Therapie. 2001 Jul-Aug;56(4):427-30.
Related Articles, Links
Preliminary evaluation of the hypoglycemic effect of some Brazilian medicinal plants.
Novaes AP, Rossi C, Poffo C, Pretti Junior E, Oliveira AE, Schlemper V, Niero R, CechinelFilho V, Burger C.
Nucleo de Investigacoes Quimico-Farmaceuticas (NIQFAR), Centro de Ensino Superior em
Ciencias da Saude (CCS), Universidade do Vale do Itajai, UNIVALI, Rua Uruguai 458, 88302202, Itajai, SC, Brazil.
The hypoglycemic effect of five Brazilian medicinal plants (Epidendrum monsenii, Marrubium
vulgare, Rheedia gardneriana, Rubus imperialis and Wedelia paludosa) was studied on alloxaninduced diabetic rats. The extract of these plants was intragastrically administered to diabetic rats.
The results showed that all plants studied (except R. gardneriana) significantly lowered the blood
glucose. These results suggest that these four medicinal plants could be an adjuvant agent in the
treatment of diabetes mellitus.
PMID: 11677867 [PubMed - indexed for MEDLINE]
19: Indian J Physiol Pharmacol. 1983 Jul-Sep;27(3):257-8.
Related Articles, Links
Hypoglycaemic activity of an indigenous drug (Gymnema sylvestre, 'Gurmar') in normal
and diabetic persons.
Khare AK, Tondon RN, Tewari JP.
Publication Types:

Letter
PMID: 6668058 [PubMed - indexed for MEDLINE]
20: J Ethnopharmacol. 1999 Nov 30;67(3):367-72.
Related Articles, Links
A comparative evaluation of some blood sugar lowering agents of plant origin.
Chattopadhyay RR.
Biometry Research Unit, Indian Statistical Institute, Calcutta.
A comparison of blood sugar lowering activity of four important medicinal plants (Azadirachta
indica, Gymnema sylvestre, Catharanthus roseus and Ocimum sanctum) were carried out against
normal and streptozotocin-induced diabetic rat models. The plant extracts decreased the blood
sugar level in varying degrees. Blood sugar lowering unit (BLU) of activity of each leaf extract
and tolbutamide was calculated by ED50 values. Statistical analysis revealed significant (P < 0.05)
variation among the treatments as well as doses with regard to their blood sugar lowering capacity.
A. indica leaf extract was found to have the most potent blood sugar-lowering activity followed by
C. roseus, G. sylvestre and O. sanctum.
PMID: 10617074 [PubMed - indexed for MEDLINE]
21: J Ethnopharmacol. 2003 Jan;84(1):105-8.
Related Articles, Links
Comparative evaluation of hypoglycaemic activity of some Indian medicinal plants in
alloxan diabetic rats.
Kar A, Choudhary BK, Bandyopadhyay NG.
Satsang Herbal Research and Analytical Laboratories, PO Satsang-814 116 Deoghar, India.
[email protected]
In our experiments 30 hypoglycaemic medicinal plants (known and less known) have been
selected for thorough studies from indigenous folk medicines, Ayurvedic, Unani and Siddha
systems of medicines. In all the experiments with different herbal samples (vacuum dried 95%
ethanolic extracts), definite blood glucose lowering effect within 2 weeks have been confirmed in
alloxan diabetic albino rats. Blood glucose values are brought down close to normal fasting level
using herbal samples at a dose of 250 mg/kg once, twice or thrice daily, as needed. While
evaluating comparative hypoglycaemic activity of the experimental herbal samples, significant
blood glucose lowering activities are observed in decreasing order in the following 24 samplesCoccinia indica, Tragia involucrata, G. sylvestre, Pterocarpus marsupium, T. foenum-graecum,
Moringa oleifera, Eugenia jambolana, Tinospora cordifolia, Swertia chirayita, Momordica
charantia, Ficus glomerata, Ficus benghalensis, Vinca rosea, Premna integrifolia, Mucuna prurita,
Terminalia bellirica, Sesbenia aegyptiaca, Azadirachta indica, Dendrocalamus hamiltonii, Zingiber
officinale, Aegle marmelos, Cinnamomum tamala, Trichosanthes cucumerina and Ocimum
sanctum. Present studies besides confirming hypoglycaemic activities of the experimental herbal
samples, help identify more potent indigenous hypoglycaemic herbs (in crude ethanolic extract)
from the comparative study of the reported experimental results. Copyright 2002 Published by
Elsevier Science Ireland Ltd.
PMID: 12499084 [PubMed - indexed for MEDLINE]
22: Altern Med Rev. 1999 Feb;4(1):46-7.
Related Articles, Links
Gymnema sylvestre.
[No authors listed]
PMID: 9988783 [PubMed - indexed for MEDLINE]
23: Arch Med Res. 1992 Spring;23(1):59-64.
Related Articles, Links
Hypoglycemic effect of plants used in Mexico as antidiabetics.
Roman Ramos R, Alarcon-Aguilar F, Lara-Lemus A, Flores-Saenz JL.
Health Sciences Department, Biological and Health Sciences Division, Metropolitan Autonomous
University, Iztapalapa Campus, Mexico City.
The objective of this work is to investigate the hypoglycemic effect of 12 "antidiabetic" plants
used in Mexico. The studies were performed using 27 healthy rabbits with the gastric
administration of water, tolbutamide or decoction of the "antidiabetic" plant before the induction
of temporary hyperglycemia by subcutaneous injection of 50% dextrose solution (4 ml/kg of
weight) at the beginning of the experiment and after 60 min. Blood glucose was determined every
60 min for a period of 5 h. Tolbutamide and eight of the studied plants decreased significantly the
hyperglycemia as compared with control test (water) (p < 0.05). The strongest effect was yielded
by Guaiacum coulteri, followed by Marrubium vulgare, Crataegus pubescens, Cynodon dactylon,
Calea zacatechichi, Buddleia americana, Bauhinia divaricata and Coix lachryma. The decrease of
hyperglycemia caused by Physalis phyladelphyca, Pavonia schiedeana and Eucaliptus globulus
was not significant (p > 0.05). Urtica dioica increased glycemia slightly.
PMID: 1308793 [PubMed - indexed for MEDLINE]
24: Pharmacol Res Commun. 1981 May;13(5):475-86.
Related Articles, Links
The insulinotropic activity of Gymnema sylvestre, R. Br. An Indian medical herb used in
controlling diabetes mellitus.
Shanmugasundaram KR, Panneerselvam C, Samudram P, Shanmugasundaram ER.
PMID: 7027275 [PubMed - indexed for MEDLINE]
25: Chem Pharm Bull (Tokyo). 1996 Feb;44(2):469-71.
Related Articles, Links
New hypoglycemic constituents in "gymnemic acid" from Gymnema sylvestre.
Murakami N, Murakami T, Kadoya M, Matsuda H, Yamahara J, Yoshikawa M.
Kyoto Pharmaceutical University, Japan.
Investigation of hypoglycemic activity of major saponin constituents from "gymnemic acid", a
crude saponin fraction of G. sylvestre, exposed not only two new saponins, gymnemosides a (1)
and b (2), but also gymnemoside b and gymnemic acid V (7) as active principles. Furthermore, an
acetyl group linked 16- or 22-hydroxy group in 1 and 2 was found to migrate easily to primary 28hydroxyl group, while acyl migration from 28-hydroxy group in 3 was little observed.
PMID: 8998848 [PubMed - indexed for MEDLINE]
26: Zhong Yao Cai. 2003 Apr;26(4):305-7.
Related Articles, Links
[Advances in the study on hypoglycemic constituents of Gymnema sylvestre (Retz.) Schult]
[Article in Chinese]
Jiang H.
Guangxi College of Traditional Chinese Medicine, Nanning, Guangxi Province, 530001
Publication Types:


Review
Review, Tutorial
PMID: 14631994 [PubMed - indexed for MEDLINE]
27: Exp Diabesity Res. 2003 Jul-Sep;4(3):183-9.
Related Articles, Links
Effect of Gymnema montanum leaves on serum and tissue lipids in alloxan diabetic rats.
Ananthan R, Latha M, Ramkumar KM, Pari L, Baskar C, Narmatha Bai V.
Department of Botany, Bharathiar University, Coimbatore, Tamil Nadu, India.
[email protected]
The effect of Gymnema montanum leaves on alloxan-induced hyperlipidemia was studied in male
Wistar rats. Ethanolic extract of G. montanum leaves was administered orally and different doses
of the extract on blood glucose, serum and tissue lipids, hexokinase, glucose-6-phosphatase,
thiobarbituric acid-reactive substances (TBARS), hydroperoxides, and glutathione in alloxaninduced diabetic rats were studied. G. montanum leaf extract (GLEt) at doses of 50, 100, 200
mg/kg body weight for 3 weeks suppressed the elevated blood glucose and lipid levels in diabetic
rats. GLEt at 200 mg/kg body weight was found to be comparable to glibenclamide, a reference
drug. These data indicate that G. montanum represents an effective antihyperglycemic and
antihyperlipidemic adjunct for the treatment of diabetes and a potential source of discovery of new
orally active agent for future therapy.
PMID: 15061646 [PubMed - in process]
28: Pharmacol Res. 2003 Dec;48(6):551-6.
Related Articles, Links
Antidiabetic effect of Gymnema montanum leaves: effect on lipid peroxidation induced
oxidative stress in experimental diabetes.
Ananthan R, Baskar C, NarmathaBai V, Pari L, Latha M, Ramkumar KM.
Department of Botany, Bharathiar University, Coimbatore 641046, Tamil Nadu, India.
[email protected]
Gymnema montanum is widely used in ancient medicine for the ailment of various diseases. Oral
administration of 200 mg kg(-1) (body weight) BW of the alcoholic extract of the leaf for 3 weeks
resulted in a significant reduction in blood glucose and an increase in plasma insulin, whereas the
effect of 50 and 100 mg kg(-1) BW was not significant. The alcoholic extract also resulted in
decreased free radical formation in plasma of diabetic rats. Thus, this study shows that Gymnema
montanum leaf extract (GLEt) possess antihyperglycemic and antiperoxidative effect. The
decrease in lipid peroxides and increase in reduced glutathione (GSH), ascorbic acid (Vitamin C)
and alpha-tocopherol (Vitamin E) clearly show the antioxidant properties of GLEt. The effect of
GLEt was most prominently seen in the case of animals given 200 mg kg(-1) BW. In addition, the
results suggest that GLEt was highly effective than the reference drug glibenclamide.
PMID: 14527818 [PubMed - in process]
29: J Ethnopharmacol. 1984 Jul;11(2):223-31.
Related Articles, Links
Oral hypoglycaemic activity of some medicinal plants of Sri Lanka.
Karunanayake EH, Welihinda J, Sirimanne SR, Sinnadorai G.
Investigations were carried out to evaluate the oral hypoglycaemic activity of some Sri Lankan
medicinal plants. Approximately 40 plants available locally are reputed to have oral
hypoglycaemic activity. Of these, the mostly widely used are (a) Salacia reticulata (Celastraceae)
(b) Aegle marmelos (Rutaceae) and (c) Momordica charantia (Cucurbitaceae). Aqueous
decoctions of these plants were investigated for their ability to lower the fasting blood glucose
level and improve the glucose tolerance in laboratory animals. The results indicate that the
aqueous decoctions of all three plants possess significant hypoglycaemic effect. The magnitude of
this effect showed time related variation with the three plants. The highest oral hypoglycaemic
activity and the maximum improvement of the oral glucose tolerance were associated with the
extract of Momordica charantia while the least but significant effects were shown by Salacia
reticulata.
PMID: 6492834 [PubMed - indexed for MEDLINE]
30: J Ethnopharmacol. 1995 Jun 23;47(1):9-26.
Related Articles, Links
Plant-derived triterpenoid sweetness inhibitors.
Suttisri R, Lee IS, Kinghorn AD.
Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of
Illinois at Chicago 60612, USA.
Considerable recent attention has been focused on naturally occurring compounds with tastemodifying activity, which are of potential use in both dietary sweetness management and in
gaining a better understanding of the sweet taste sensation. This review summarizes information
on the phytochemistry and biological activity of more than 40 triterpenoid sweetness inhibitors
that have been isolated from the leaves of three medicinal plants, namely, Gymnema sylvestre
R.Br. (Asclepiadaceae), Ziziphus jujuba P. Miller (Rhamnaceae), and Hovenia dulcis Thunb.
(Rhamnaceae).
Publication Types:


Review
Review, Tutorial
PMID: 7564423 [PubMed - indexed for MEDLINE]
31: Biochem Soc Trans. 1979 Feb;7(1):99-102.
Related Articles, Links
An introduction to the control of carbohydrate metabolism: possible sites for
pharmacological intervention in hyperglycaemia.
Sherratt HS, Hue L.
PMID: 437303 [PubMed - indexed for MEDLINE]
32: J Pharm Sci. 1967 Jun;56(6):732-6.
Related Articles, Links
Constituents from Gymnema sylvestre leaves. II. Nitrogenous compounds.
Sinsheimer JE, McIlhenny HM.
PMID: 6039815 [PubMed - indexed for MEDLINE]
33: J Pharm Sci. 1965 Oct;54(10):1541-4.
Related Articles, Links
Constituents from Gymnema sylvestre leaves.
Manni PE, Sinsheimer JE.
PMID: 5883239 [PubMed - indexed for MEDLINE]
34: J Med Food. 2003 Spring;6(1):43-9.
Related Articles, Links
Effect of Gymnema montanum on blood glucose, plasma insulin, and carbohydrate
metabolic enzymes in alloxan-induced diabetic rats.
Ananthan R, Latha M, Pari L, Ramkumar KM, Baskar CG, Bai VN.
Department of Botany, Bharathiar University, Coimbatore-641 046, Tamil Nadu, India.
The effects of Gymnema montanum, an endangered plant used in the ancient period of India, on
blood glucose, plasma insulin, and carbohydrate metabolic enzymes were studied in alloxan
diabetic rats. Administration of alcoholic extract of G. montanum leaves (50, 100, 200 mg/kg
body weight) to alloxan diabetic rats for 3 weeks reduced the blood glucose level. Administration
of G. montanum leaf extract (GLEt) at 200 mg/kg body weight significantly decreased the blood
glucose levels and significantly increased the plasma insulin levels. This clearly shows the
antidiabetic efficacy of GLEt, which was better than that of glibenclamide.
PMID: 12804019 [PubMed - indexed for MEDLINE]
35: J Ethnopharmacol. 1983 Mar;7(2):205-34.
Related Articles, Links
Enzyme changes and glucose utilisation in diabetic rabbits: the effect of Gymnema sylvestre,
R.Br.
Shanmugasundaram KR, Panneerselvam C, Samudram P, Shanmugasundaram ER.
The administration of the dried leaf powder of Gymnema sylvestre regulates the blood sugar levels
in alloxan diabetic rabbits. G. sylvestre therapy not only produced blood glucose homeostasis but
also increased the activities of the enzymes affording the utilisation of glucose by insulin
dependent pathways: it controlled phosphorylase levels, gluconeogenic enzymes and sorbitol
dehydrogenase. The uptake and incorporation of [14C] glucose into the glycogen and protein are
increased in the liver, kidney and muscle in G. sylvestre administered diabetic animals when
compared to the untreated diabetic animals. Pathological changes initiated in the liver during the
hyperglycemic phase are reversed by controlling hyperglycemia by G. sylvestre. G. sylvestre, a
herb used for the control of diabetes mellitus in several parts of India, appears to correct the
metabolic derangements in diabetic rabbit liver, kidney and muscle.
PMID: 6865451 [PubMed - indexed for MEDLINE]
36: Therapie. 2001 Jul-Aug;56(4):427-30.
Related Articles, Links
Preliminary evaluation of the hypoglycemic effect of some Brazilian medicinal plants.
Novaes AP, Rossi C, Poffo C, Pretti Junior E, Oliveira AE, Schlemper V, Niero R, CechinelFilho V, Burger C.
Nucleo de Investigacoes Quimico-Farmaceuticas (NIQFAR), Centro de Ensino Superior em
Ciencias da Saude (CCS), Universidade do Vale do Itajai, UNIVALI, Rua Uruguai 458, 88302202, Itajai, SC, Brazil.
The hypoglycemic effect of five Brazilian medicinal plants (Epidendrum monsenii, Marrubium
vulgare, Rheedia gardneriana, Rubus imperialis and Wedelia paludosa) was studied on alloxaninduced diabetic rats. The extract of these plants was intragastrically administered to diabetic rats.
The results showed that all plants studied (except R. gardneriana) significantly lowered the blood
glucose. These results suggest that these four medicinal plants could be an adjuvant agent in the
treatment of diabetes mellitus.
PMID: 11677867 [PubMed - indexed for MEDLINE]
37: Indian J Physiol Pharmacol. 1983 Jul-Sep;27(3):257-8.
Related Articles, Links
Hypoglycaemic activity of an indigenous drug (Gymnema sylvestre, 'Gurmar') in normal
and diabetic persons.
Khare AK, Tondon RN, Tewari JP.
Publication Types:

Letter
PMID: 6668058 [PubMed - indexed for MEDLINE]
38: J Ethnopharmacol. 1999 Nov 30;67(3):367-72.
Related Articles, Links
A comparative evaluation of some blood sugar lowering agents of plant origin.
Chattopadhyay RR.
Biometry Research Unit, Indian Statistical Institute, Calcutta.
A comparison of blood sugar lowering activity of four important medicinal plants (Azadirachta
indica, Gymnema sylvestre, Catharanthus roseus and Ocimum sanctum) were carried out against
normal and streptozotocin-induced diabetic rat models. The plant extracts decreased the blood
sugar level in varying degrees. Blood sugar lowering unit (BLU) of activity of each leaf extract
and tolbutamide was calculated by ED50 values. Statistical analysis revealed significant (P < 0.05)
variation among the treatments as well as doses with regard to their blood sugar lowering capacity.
A. indica leaf extract was found to have the most potent blood sugar-lowering activity followed by
C. roseus, G. sylvestre and O. sanctum.
PMID: 10617074 [PubMed - indexed for MEDLINE]
39: J Ethnopharmacol. 2003 Jan;84(1):105-8.
Related Articles, Links
Comparative evaluation of hypoglycaemic activity of some Indian medicinal plants in
alloxan diabetic rats.
Kar A, Choudhary BK, Bandyopadhyay NG.
Satsang Herbal Research and Analytical Laboratories, PO Satsang-814 116 Deoghar, India.
[email protected]
In our experiments 30 hypoglycaemic medicinal plants (known and less known) have been
selected for thorough studies from indigenous folk medicines, Ayurvedic, Unani and Siddha
systems of medicines. In all the experiments with different herbal samples (vacuum dried 95%
ethanolic extracts), definite blood glucose lowering effect within 2 weeks have been confirmed in
alloxan diabetic albino rats. Blood glucose values are brought down close to normal fasting level
using herbal samples at a dose of 250 mg/kg once, twice or thrice daily, as needed. While
evaluating comparative hypoglycaemic activity of the experimental herbal samples, significant
blood glucose lowering activities are observed in decreasing order in the following 24 samples-
Coccinia indica, Tragia involucrata, G. sylvestre, Pterocarpus marsupium, T. foenum-graecum,
Moringa oleifera, Eugenia jambolana, Tinospora cordifolia, Swertia chirayita, Momordica
charantia, Ficus glomerata, Ficus benghalensis, Vinca rosea, Premna integrifolia, Mucuna prurita,
Terminalia bellirica, Sesbenia aegyptiaca, Azadirachta indica, Dendrocalamus hamiltonii, Zingiber
officinale, Aegle marmelos, Cinnamomum tamala, Trichosanthes cucumerina and Ocimum
sanctum. Present studies besides confirming hypoglycaemic activities of the experimental herbal
samples, help identify more potent indigenous hypoglycaemic herbs (in crude ethanolic extract)
from the comparative study of the reported experimental results. Copyright 2002 Published by
Elsevier Science Ireland Ltd.
PMID: 12499084 [PubMed - indexed for MEDLINE]
1: J Pak Med Assoc. 1988 Nov;38(11):289-95.
Related Articles, Links
Effect of Grewia asiatica, Gossypium herbacium and Gymnema sylvestre on blood glucose,
cholesterol and triglycerides levels in normoglycaemic and alloxan diabetic rabbits.
Dogar IA, Ali M, Yaqub M.
PMID: 3148751 [PubMed - indexed for MEDLINE]
2: Diabetes Res Clin Pract. 1995 Jul;29(1):11-7.
Related Articles, Links
Effects of seishin-renshi-in and Gymnema sylvestre on insulin resistance in streptozotocininduced diabetic rats.
Tominaga M, Kimura M, Sugiyama K, Abe T, Igarashi K, Igarashi M, Eguchi H, Sekikawa
A, Ogawa A, Manaka H, et al.
Third Department of Internal Medicine, Yamagata University School of Medicine, Japan.
Although there is no concept of insulin resistance in traditional Kampo (Chinese) medicine and
Indian medicine, we had the hypothesis that some drug in a mixture of crude drugs which was
believed to ameliorate diabetes mellitus may have had the effect of improving insulin resistance.
To test this hypothesis, the effects of Seishin-renshi-in (Chinese medicine) and Gymnema
sylvestre (Indian medicine) on the insulin resistance of streptozotocin-induced diabetic rats was
studied by the glucose clamp technique. Oral administration of Seishin-renshi-in (800 mg/kg/day)
with injections of a minimum dose of Ultralente insulin decreased urine volume and urinary
glucose excretion during a 7-day treatment period and improved the insulin stimulated glucose
uptake in peripheral tissues, as well as improving the insulin suppressed hepatic glucose output
during glucose clamp. However, G. sylvestre (120 mg/kg/day) treatment did not improve insulin
resistance. We conclude that Seishin-renshi-in, with a small dose of insulin, improved insulin
resistance in streptozotocin-induced diabetic rats, but Gymnema sylvestre did not.
PMID: 8593754 [PubMed - indexed for MEDLINE]
3: Comp Biochem Physiol A. 1972 Oct 1;43(2):381-91.
Related Articles, Links
Comparative electrocardiography in lizards: effects of temperature and Gymnema sylvestre
fractions.
Yackzan KS, Yousef MK, Dill DB.
PMID: 4145248 [PubMed - indexed for MEDLINE]
4: Bull Calcutta Sch Trop Med. 1966 Oct;14(4):126-7.
Crystalline saponin from Gymnema sylvestre.
Chakravarti RN, Chakravarti D, Itty MI.
PMID: 6003983 [PubMed - indexed for MEDLINE]
Related Articles, Links