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TAURINE SUPPLEMENTATION AND
PANCREATIC REMODELING
Abdeslem El Idrissi 1,2, Latifa Boukarrou1 and William L’Amoreaux1,2
1
Department of Biology, College of Staten Island, 2City University of New
York Graduate School, NY
Abstract
Taurine is a semi-essential sulphur containing amino acid derived from
methionine and cysteine metabolism. Taurine has several biological processes such as hypoglycemic action, antioxidation, and detoxification. In
this study we evaluated the role of taurine in pancreatic islets development, since the endocrine pancreas undergoes significant modifications
during neonatal life. Histological examination of the pancreas from taurinefed mice revealed no histological abnormalities in the endocrine or exocrine parts of the pancreas. However, supplementation of taurine in the
drinking water resulted in a drastic and significant increase in the number
of islets per section. Furthermore, islets size was significantly larger. We
hypothesize that supplementation of taurine, which is important for the development of the endocrine pancreas may reduce cytokine-induced apoptosis in pancreatic beta cells.
The endocrine pancreas undergoes significant modifications during neonatal life and apoptosis is an important mechanism in this remodeling.
We suggest that alteration of this remodeling process during this period of
time, when a fine balance between cell replication and cell death is critical,
would affect the development of the pancreatic islets of Langerhans, and
could have important effects on the pancreatic cell mass and the endocrine function.
Abbreviations: PCNA, proliferating cell nuclear antigen; Tau, taurine;
GAD, glutamic acid decarboxylase; iNOS, inducible nitric oxide synthase;
IGF, insulin-like growth factor; WT, wild type controls
Taurine 8: Physiological roles and mechanisms of action
Edited by Abdeslem El Idrissi et al. Springer, New York 2012
2 Abdeslem El Idrissi et al.
1.1 INTRODUCTION
Taurine (2-aminoethanesulfonic acid) is a sulfur-containing amino acid. It
is one of the most abundant free amino acids in many excitable tissues, including the brain, skeletal and cardiac muscles. Physiological actions of
taurine are widespread and include bile acid conjugation, detoxification,
membrane stabilization, osmoregulation, neurotransmission, and modulation of cellular calcium levels (Lambardini 1985; Solis et al. 1988; Foos
and Wu 2002; Saransaari and Oja 2000; Schaffer et al. 2000). Furthermore, taurine plays an important role in modulating glutamate and GABA
neurotransmission (Militante and Lombardini 1998; El Idrissi and
Trenkner 1999; 2004). We have previously shown that taurine prevents
excitotoxicity in vitro primarily through modulation of intracellular calcium homeostasis (El Idrissi and Trenkner 1999). In neurons, calcium plays
a key role in mediating glutamate excitotoxicity. Taurine is added to milk
formula and in solution for parenteral nutrition of premature babies to prevent retinal degeneration and cholestasis (Huxtable 1992; Lorenco and
Camilo 2002). More recently, it has been shown that gestational taurine is
able to prevent pancreatic alterations induced by gestational malnutrition
especially low-protein diet (Dahri et al. 1991; Cherif et al. 1996; Merezak
et al. 2001; Boujendar et al. 2002). In addition, taurine administration during gestation delays the mean onset time of diabetes in NOD mice (Arany
et al. 2004); whereas taurine supplementation on dams fed with normal diet produces weak glucose intolerance, and increases islet sensitivity to cytokines in offspring (Merezak et al. 2001). Moreover, taurine plays a role
in glucose metabolism in adults (Hansen 2001; Franconi et al. 2006).
1.2 METHODS
1.2.1 Quantification of size and number of pancreatic islets
Two months old mice were perfused with 4% paraformaldehyde and
pancreas were isolated attached the pyloric region of the stomach and the
duodenum. The initial part of the duodenum served to orient the pancreas
for the sectional plane. Tissue was cryoprotected with 30% sucrose and
cryosectioned at a thickness of 15 µm. Sections were stained with hematoxylin and eosin. Contiguous sections were stained with propidium iodide
to visualize condensed chromatin as an indication of apoptotic cell death.
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Taurine and pancreatic remodeling 3
microscopy was performed by histologist unaware of the treatment conditions.
1.2.2 Statistic analysis
Statistical significance was determined by Student's t-test. Each value was
expressed as the mean ± SEM. Differences were considered statistically
significant when the calculated P value was less than 0.05.
1.3 RESULTS
1.3.1 Taurine supplementation increases the size and number
of the Islets of Langerhans
In this study we examined the effects of taurine supplementation on
pancreatic remodeling. Mice were supplemented with taurine (0.05%) in
drinking water at the age of four weeks and remained on this diet for an
additional for weeks. When mice were two months old, pancreas were removed and processed for histology. Pancreata were dissected attached to
the pyloric region of the stomach and the duodenum. The initial part of the
duodenum served to orient the pancreas for the sectional plane. The pancreas of mice is not encapsulated in connective tissue, and it was difficult
to isolate the pancreas without the surrounding adipose tissue of the peritoneum. Each pancreas yielded approximately 150 sections. Quantification
of the number of islets was based on determining the number of islets per
section. Histological examination of pancreas from taurine-fed mice revealed a significant increase in their size (Fig. 1). The pancreas from these
mice did not seem to be enlarged and the exocrine serous acini were of
normal histology when compared to the control pancreas. Interestingly
however, the number of islets was significantly increased (Fig. 2). On average, a pancreas from control mice yielded approximately 4 islets per section, whereas a pancreas of taurine-fed mice contained more than 10 islets.
The number of islets per section was not uniform throughout the pancreas,
but differences in islets size and number between controls and taurine-fed
mice was maintained proportionally throughout the different regions of the
pancreas.
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14
12
Islets of Langerhan / section
10
8
6
4
2
0
WT
WT Tau
Fig. 1. Taurine induces an increase in the number of islets in the pancreas. All
mice were 2 months old. Taurine (0.05%) was supplemented in the drinking water
for 4 weeks. control, n=4; Tau, n=5. Pancreata were crysectioned (15 um) and
stained with hematoxylin and Eosin. Each pancreas yielded approximately 150
sections. All pancreata were cut in the longitudinal plane. Supplementation of taurine to mice caused a significant increase in the size and number of islets
(p< .001).
1.4 Discussion
Histological examination of the pancreas revealed that taurine-fed mice
had a significant increase in the size of islets of Langerhans when compared to controls. The overall size of the pancreas was not affected. There
were no histological abnormalities in the endocrine or exocrine parts of the
pancreas. Surprisingly, supplementation of taurine in the drinking water
resulted in a drastic and significant increase in the number of islets per section. Previously, it has been reported that the islets from taurine treated
mice had almost double the number of cells immunopositive for proliferating cell nuclear antigen (PCNA). This increase proliferation was accompanied by a reduction in the incidence of apoptosis in islet cells, and also a
significant increase in the number of islet cells immunopositive for IGF-II
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Taurine and pancreatic remodeling 5
(Arany et al. 2004). We have supplemented taurine in the drinking water
shortly after weaning of mice. It has been shown that a peak of islet cell
apoptosis is maximal in the pancreas 14 days after birth and is temporally
associated with a fall in the islet cell expression of IGF-II (Petril et al.
1998). IGF-II was shown to function as an islet survival factor in vitro.
The induction of islet cell apoptosis in vivo may involve an increased expression of inducible nitric oxide synthase (iNOS) within ß cells. Interestingly, taurine as been shown to be a potent inhibitor of iNOS (Liu et al.,
1998). Similarly, Scaglia et al., (1997) have shown decreased replication
and increased incidence of apoptosis in the ß cells in the presence of IGFII. These data show that the endocrine pancreas undergoes significant
modification during neonatal life and that apoptosis is an important mechanism in this remodeling. Dysregulation of this remodeling process during
this period of time when a fine balance between cell replication and cell
death determines the development of the islets of Langerhans in the pancreas and could have important effects on the pancreatic cell mass and the
endocrine function.
1.5 CONCLUSION
In summary, this study shows that supplementation of taurine in the drinking water resulted in a significant increase in the size and number of the islets of Langerhans. These histological effects of taurine on the pancreas
are consistent with the hypoglycemic effects of taurine and may have implication in diabetes.
1.6 ACKNOWLEDGEMENTS
We thank Ekaterina Zavyalova, George Malliaros, Candice Cruz and
Labentina Shala for helping with the histological evaluation and staining
of tissue. This work was supported by PSC-CUNY and CSI.
1.7 REFERENCES
Arany E, Strutt B, Romanus P, Remacle C, Reusens B, Hill DJ (2004) Taurine
supplement in early life altered islet morphology, decreased insulitis and delayed the onset of diabetes in non-obese diabetic mice, Diabetologia 47:1831–
1837
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Schaffer S, Takahashi K, Azuma J (2000) Role of osmoregulation in the actions of
taurine. Amino Acids 19:527-546
Solis JM, Herranz AS, Erreras O, Lerma J, Martin del Rio R (1988) Does taurine
act as an osmoregulatory substance in the rat brain. Neurosci Lett 91:53-58
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