Download Lecture 11 th week

Department of medical physiology
11th week
Semester: summer
Study program: Dental medicine
Lecture: RNDr. Soňa Grešová, PhD.
1. Pancreas Hormones
2. Pituitary Hormones and their
control by the hypothalamus
Pancreas
• Hormones:
– Insulin
– Glucagon
– Amylin
– Somatostatin
– Pancreatic polypeptide
Anatomy of the Pancreas
• is composed of two major
types of tissues:
1) the acini (digestive juices)
2) the islets of Langerhans
(insulin and glucagon)
• three major types of cells,
–
–
–
–
alpha, (25%, glucagon)
beta, (60%, insulin, amylin)
delta cells (10%, somatostatin
PP cells (pancreatic
polypeptide)
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and
Hall textbook of medical physiology. Philadelphia, PA:
Saunders Elsevier.
Cell-to-cell communication and direct
control of secretion
• Insulin inhibits glucagon secretion,
• Amylin inhibits insulin secretion,
• Somatostatin inhibits the secretion of both
insulin and glucagon
Insulin
• Insulin and its metabolic effects
– insulin affects fat and protein metabolism almost as much as it
does carbohydrate metabolism
• Insulin is a hormone associated with energy abundance
– excess amounts of carbohydrates = insulin is secreted in great
quantity
– insulin plays an important role in storing the excess energy
(glycogen = liver, muscles)
– excess carbohydrates that cannot be stored as glycogen are
converted under the stimulus of insulin into fats and stored in
the adipose tissue
– insulin has a direct effect in conversion of amino acids into
protein (inhibits the breakdown of the proteins that are already
in the cells)
Insulin synthesis
• Insulin is synthesized in the beta cells
• with translation of the insulin RNA by ribosomes attached
to the endoplasmic reticulum to form an insulin
preprohormone
• is then cleaved in the endoplasmic reticulum to form a
proinsulin
• this is further cleaved in the Golgi apparatus to form insulin
and peptide fragments before being packaged in the
secretory granules
• insulin is secreted into the blood in an unbound form (halflife -6 minutes, cleared from the circulation within 10 to 15
minutes)
• is degraded by the enzyme insulinase mainly in the liver, to
a lesser extent in the kidneys and muscles, and slightly in
most other tissues
Activation of target cell receptors by
Insulin
• insulin binds and activates a
membrane receptor protein
• binds with the alpha subunits
on the outside of the cell
• the beta subunits protruding
into the cell become
autophosphorylated
• the receptor activates a local
tyrosine kinase phosphorylation of multiple
other intracellular enzymes
• effects on carbohydrate, fat,
and protein metabolism
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of
medical physiology. Philadelphia, PA: Saunders Elsevier.
Effect of insulin on carbohydrate
metabolism
• The insulin in turn causes rapid
uptake, storage, and use of
glucose by almost all tissues of
the body, but especially by the
muscles, adipose tissue, and
liver
• Insulin promotes muscle
glucose uptake and
metabolism
– Storage of glycogen in muscle
– The glycogen can later be used
for energy by the muscle
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and
Hall textbook of medical physiology. Philadelphia, PA:
Saunders Elsevier.
Effect of insulin on carbohydrate
metabolism
• Insulin promotes liver uptake, storage, and use
of glucose
– Insulin inactivates liver phosphorylase
– Insulin increasing the activity of the enzyme
glucokinase
– Insulin also increases the activities of the enzymes
especially glycogen synthase
The net effect of all these actions is to increase the
amount of glycogen in the liver
– Glucose is released from the liver between meals
• The decreasing blood glucose causes the pancreas to
decrease its insulin secretion
• then reverses all the effects for glycogen storage
Effect of insulin on carbohydrate
metabolism
• Insulin promotes conversion of excess glucose
into fatty acids and inhibits gluconeogenesis in
the liver
– Insulin promotes conversion of excess glucose into
fatty acids = packaged as VLDL - transported to the
adipose tissue and deposited as FAT
– inhibits gluconeogenesis in the liver by decreasing the
quantities and activities of the liver enzymes required
for gluconeogenesis
Effect of insulin on carbohydrate
metabolism
• Lack of effect of insulin on glucose uptake
and usage by the brain
– the brain cells are permeable to glucose and can
use glucose without the intermediation of insulin
(retina, germinal epithelium of the gonads)
Effect of insulin on fat metabolism
• Insulin promotes fat synthesis and storage
– Insulin increases the transport of glucose into the liver
cells (The glucose is first split to pyruvate in the
glycolytic pathway, and the pyruvate subsequently is
converted to acetyl coenzyme A (acetyl-CoA), the
substrate from which fatty acids are synthesized
– Most of the fatty acids are then synthesized within the
liver itself and used to form triglycerides
• Role of insulin in storage of fat in the adipose
cells
– Insulin inhibits the action of hormone-sensitive lipase
– Insulin promotes glucose transport through the cell
membrane into the fat cells
Effect of insulin on fat metabolism
• Insulin deficiency increases
use of fat for energy
– Insulin deficiency causes
lipolysis of storage fat and
release of free fatty acids
– Insulin deficiency increases
plasma cholesterol and
phospholipid
concentrations
– Excess usage of fats during
insulin lack causes ketosis
and acidosis
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall
textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Effect of Insulin on protein
metabolism and on growth
• Insulin promotes protein synthesis and storage
– Insulin stimulates transport of many of the amino
acids into the cells (valine, leucine, isoleucine,
tyrosine, phenylalanine)
– Insulin increases the translation of messenger RNA,
– insulin also increases the rate of transcription of
selected DNA genetic sequences
– Insulin inhibits the catabolism of proteins
– In the liver, insulin depresses the rate of
gluconeogenesis
Mechanisms of insulin secretion by
the pancreatic beta cells
• glucose transporters (GLUT- 2)
• glucose is phosphorylated to
glucose-6-phosphate by
glucokinase
• Oxidation to form adenosine
triphosphate (ATP)
• Inhibition the ATP-sensitive
potassium channels
• opening voltage-gated calcium
channels,
• fusion of the docked insulincontaining vesicles
• secretion of insulin into the
extracellular fluid by exocytosis
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and
Hall textbook of medical physiology. Philadelphia, PA:
Saunders Elsevier.
Control of insulin secretion
• Increased blood glucose stimulates insulin secretion
• Feedback relation between blood glucose
concentration and insulin secretion rate
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall textbook of medical physiology. Philadelphia, PA: Saunders Elsevier.
Control of insulin secretion
• Other factors that stimulate insulin secretion
– Amino acids (arginine, lysine)
– Gastrointestinal hormones (gastrin, secretin,
cholecystokinin, incretins)
• Other hormones and the autonomic nervous system
– glucagon, growth hormone, cortisol, and, to a lesser
extent, progesterone and estrogen
– Parasympathetic – increase insulin secretion during
hypeglycemic conditions
– Symphatetic – increase glucagon secretion and decrease
insulin secretion during hypoglycemia
• Epinephrine is especially important in increasing plasma glucose
concentration, far greater increases fatty acids during periods of
stress
Control of insulin secretion
• Glucose concentrations are believed to be
detected by specialized neurons of the
hypothalamus and brain stem, as well as by
glucose-sensing cells in peripheral locations
such as the liver
Glucagon and its functions
• Glucagon, a hormone secreted by the alpha
cells of the islets of Langerhans
• several functions that are diametrically
opposed to those of insulin
– increases the blood glucose concentration
• glucagon is also called the hyperglycemic
hormone
Glucagon and its functions
• Effects on glucose metabolism
1) breakdown of liver glycogen (glycogenolysis)
–
–
–
–
–
–
–
–
1. Glucagon activates adenylyl cyclase in the hepatic cell membrane,
2. the formation of cyclic adenosine monophosphate,
3. activates protein kinase regulator protein,
4. activates protein kinase,
5. activates phosphorylase b kinase,
6. converts phosphorylase b into phosphorylase a,
7. promotes the degradation of glycogen into glucose-1-phosphate,
8. which then is dephosphorylated; and the glucose is released from
the liver cells
2) increased gluconeogenesis in the liver
– by activating multiple enzymes that are required for amino acid
transport and gluconeogenesis in the liver, (converting pyruvate to
phosphoenolpyruvate)
Glucagon and its functions
• Other effects of glucagon
– activates adipose cell lipase, making increased quantities
of fatty acids available to the energy systems of the body
– Inhibits the storage of triglycerides in the liver
• Very high concentrations of glucagon
– 1) enhances the strength of the heart;
– 2) increases blood flow in some tissues, especially the
kidneys;
– 3) enhances bile secretion;
– 4) inhibits gastric acid secretion
Regulation of glucagon secretion
– Increased blood glucose
inhibits glucagon secretion
– Increased blood amino
acids stimulate glucagon
secretion (alanine,
arginine) – rapid
conversion of AA to
glucose
– Exercise stimulates
glucagon secretion
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall
textbook of medical physiology. Philadelphia, PA: Saunders
Elsevier.
Regulation of glucagon secretion
• Somatostatin inhibits glucagon and
insulin secretion
– The delta cells of the islets of Langerhans secrete
the hormone somatostatin
• Somatostatin acts locally within the islets of Langerhans
themselves to depress the secretion of both insulin and
glucagon
• Somatostatin decreases the motility of the stomach,
duodenum, and gallbladder
• Somatostatin decreases both secretion and absorption
in the gastrointestinal tract
Diabetes Mellitus
1. Type I diabetes, also called insulin-dependent
diabetes mellitus (IDDM), is caused by lack of
insulin secretion
2. Type II diabetes, also called non–insulindependent diabetes mellitus (NIDDM), is caused
by decreased sensitivity of target tissues to the
metabolic effect of insulin. This reduced
sensitivity to insulin is often called insulin
resistance.
Pituitary Hormones and their
control by the hypothalamus
Pituitary gland (hypophysis)
• The anterior pituitary
gland
(adenohypophysis)
– Six important peptide
hormones plus several
less important ones
• Posterior pituitary
gland
(neurohypophysis)
– two important peptide
hormones
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall
textbook of medical physiology. Philadelphia, PA: Saunders
Elsevier.
Pituitary gland (hypophysis)
• The hormones of the anterior
pituitary play major roles in the
control of metabolic functions
throughout the body
– Growth hormone
– Adrenocorticotropin (corticotropin
– Thyroid-stimulating hormone
(thyrotropin)
– Prolactin
– two separate gonadotropic
hormones, follicle-stimulating
hormone and luteinizing hormone,
• The two hormones secreted by
the posterior pituitary play other
roles
– Antidiuretic hormone (vasopressin
– Oxytocin
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall
textbook of medical physiology. Philadelphia, PA: Saunders
Elsevier.
Anterior pituitary gland
• five cell types are:
1. Somatotropes—human growth
hormone (hGH)
2. Corticotropes—
adrenocorticotropin (ACTH)
3. Thyrotropes—thyroid-stimulating
hormone (TSH)
4. Gonadotropes—gonadotropic
hormones, which include both
luteinizing hormone (LH) and
folliclestimulating hormone (FSH)
5. Lactotropes—prolactin (PRL)
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and
Hall textbook of medical physiology. Philadelphia, PA:
Saunders Elsevier.
Posterior pituitary hormones
• The bodies of the cells are large neurons,
called magnocellular neurons, located in the
supraoptic and paraventricular nuclei of the
hypothalamus
• The hormones are then transported in the
axoplasm of the neurons’ to the posterior
pituitary gland
Hypothalamus controls
pituitary secretion
• Secretion from the posterior
pituitary is controlled by
nerve signals that originate
in the hypothalamus and
terminate in the posterior
pituitary
• Secretion by the anterior
pituitary is controlled by
hormones called
hypothalamic releasing and
hypothalamic inhibitory
hormones (or factors) blood
vessels = hypothalamichypophysial portal vessels
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and
Hall textbook of medical physiology. Philadelphia, PA:
Saunders Elsevier.
Hypothalamic-Hypophysial portal
blood vessels of the anterior pituitary gland
• Hypothalamic releasing
and inhibitory hormones
are secreted into the
median eminence and
tuber cinereum, an
extension of
hypothalamic tissue into
the pituatory stalk
– tissue fluid
– sinuses of the anterior
pituitary
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and
Hall textbook of medical physiology. Philadelphia, PA:
Saunders Elsevier.
Hypothalamic-Hypophysial portal
blood vessels of the anterior pituitary gland
• Hypothalamic releasing
hormons
– Preoptic nc. release:
• Gonadotropin-releasing
hormone (GnRH), which causes
release in anterior pituitary
(basophilic cells) of the two
gonadotropic hormones,
luteinizing hormone and folliclestimulating hormone
• Male - spermatogenesis,
production of testosteron
• Female – oogenesis, ovulation,
production estrogen and
pregesteron
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and
Hall textbook of medical physiology. Philadelphia, PA:
Saunders Elsevier.
Hypothalamic-Hypophysial portal
blood vessels of the anterior pituitary gland
• Hypothalamic releasing and
inhibitory hormon
– Ventromedial nc. release:
• Growth hormone–releasing
hormone (GHRH), which causes
release of growth hormone,
and growth hormone inhibitory
hormone (GHIH), called
somatostatin, to the anterior
pituitary (acidophilic cells)
which inhibits release of growth
hormone
• Growth hormone acts directly
from blood and in liver is made
somatomedin
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall
textbook of medical physiology. Philadelphia, PA: Saunders
Elsevier.
Hypothalamic-Hypophysial portal
blood vessels of the anterior pituitary gland
• Hypothalamic releasing
hormons
– Paraventricular nc. release:
• Thyrotropin-releasing
hormone (TRH), which causes
release of thyroid-stimulating
hormone (TSH) from anterior
pituitary (basophilic cells) T3, T4
• Corticotropin-releasing
hormone (CRH), which causes
release of adrenocorticotropin
(ACTH) (basophilic cells) –
glucocorticoids (adrenal cortexzona fasciculata)
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall
textbook of medical physiology. Philadelphia, PA: Saunders
Elsevier.
Hypothalamic-Hypophysial portal
blood vessels of the anterior pituitary gland
• Hypothalamic inhibitory
hormons
– Arcuate nc. release:
• Prolactin inhibitory hormone
(PIH) dopamin, which causes
inhibition of prolactin
secretion (acidophilic cells)
– Increase production of milk
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall
textbook of medical physiology. Philadelphia, PA: Saunders
Elsevier.
Physiological functions
of growth hormone
• Growth hormone
(somatotropic hormone or
somatotropin) promotes
growth of many body tissues
– it promotes increased sizes of
the cells and increased
mitosis, with development of
greater numbers of cells and
specific differentiation of
certain types of cells such as
bone growth cells and early
muscle cells
– Growth hormone enhances
body protein, decreases fat
stores, and conserves
carbohydrates
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall
textbook of medical physiology. Philadelphia, PA: Saunders
Elsevier.
Physiological functions
of growth hormone
• Growth hormone enhances almost all facets of amino
acid uptake and protein synthesis by cells, while at the
same time reducing the breakdown of proteins
• Metabolic effects:
– Growth hormone promotes protein deposition in tissues
• Enhancement of amino acid transport through the cell
membranes
– increasing protein synthesis
• Enhancement of RNA translation to cause protein synthesis by the
ribosomes
– even AA concentrations are not increased
• Increased nuclear transcription of DNA to form RNA
– if sufficient energy, amino acids, vitamins, and other requisites for growth
are available
• Decreased catabolism of protein and amino acids
– Mobilizes large quantities of free fatty acids from the adipose tissue
(energy)
Physiological functions
of growth hormone
• Metabolic effects:
– Growth hormone enhances fat utilization for
energy
• has a specific effect in causing the release of fatty acids
from adipose tissue
– increasing the concentration of fatty acids in the body fluids
• Enhances the conversion of fatty acids to acetyl
coenzyme A (acetyl-CoA)
– its subsequent utilization for energy
• Excessive mobilization of fat from the adipose tissue
frequently causes ketosis and a fatty liver
Physiological functions
of growth hormone
• Metabolic effects:
– Growth hormone decreases carbohydrate
utilization
• 1) decreased glucose uptake in tissues such as skeletal
muscle and fat,
• 2) increased glucose production by the liver,
• 3) increased insulin secretion
• Necessity of insulin and carbohydrate for the growthpromoting action of growth hormone
– adequate insulin activity and adequate availability of
carbohydrates are necessary for growth hormone to be
effective
Physiological functions
of growth hormone
• Metabolic effects:
– Growth hormone stimulates cartilage and bone
growth
• 1) Increased deposition of protein by the chondrocytic
and osteogenic cells that cause bone growth,
• 2) Increased rate of reproduction of these cells,
• 3) a specific effect of converting chondrocytes into
osteogenic cells, thus causing deposition of new bone
Physiological functions
of growth hormone
• Metabolic effects:
– Growth hormone exerts
much of its effect through
intermediate substances
called “somatomedins” (also
called “insulin-like growth
factors”)
• Growth hormon in liver
releasing of somatomedins
• Short duration of action of
growth hormone but
prolonged action of
somatomedin C (bounded
with plasma proteins)
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall
textbook of medical physiology. Philadelphia, PA: Saunders
Elsevier.
Regulation of growth
hormone secretion
• Growth hormone is secreted in a
pulsatile pattern, increasing and
decreasing
• person’s state of nutrition or
stress - stimulate secretion
• 1) starvation, especially with
severe protein deficiency;
• 2) hypoglycemia or low
concentration of fatty acids in the
blood;
• 3) exercise;
• 4) excitement;
• 5) trauma
• 6) ghrelin
• Growth hormone increases
during the first 2 hours of deep
sleep
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall
textbook of medical physiology. Philadelphia, PA: Saunders
Elsevier.
Regulation of growth
hormone secretion
• Role of the hypothalamus
in the control of growth
hormone secretion
– growth hormone–
releasing hormone,
– growth hormone
inhibitory hormone somatostatin
– are transported to the
anterior pituitary gland
through the hypothalamichypophysial portal vessels
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and
Hall textbook of medical physiology. Philadelphia, PA:
Saunders Elsevier.
Abnormalities of growth
hormone secretion
•
Panhypopituitarism
–
•
Dwarfism
–
•
–
–
the acidophilic, growth hormone–producing cells of the anterior pituitary gland become excessively active, and
sometimes even acidophilic tumors occur in the gland
the condition occurs before adolescence, before the epiphyses of the long bones have become fused with the shafts,
height increases so that the person becomes a giant— up to 8 feet tall
diabetes mellitus
Acromegaly
–
–
•
The general effects:
• 1) hypothyroidism,
• 2) depressed production of glucocorticoids by the adrenal glands,
• 3) suppressed secretion of the gonadotropic hormones so that sexual functions are lost
Gigantism
–
•
result from generalized deficiency of anterior pituitary secretion (panhypopituitarism) during childhood
Panhypopituitarism in the Adult
–
•
This term means decreased secretion of all the anterior pituitary hormones (present from birth)
an acidophilic tumor occurs after adolescence— that is, after the epiphyses of the long bones have fused with the
shafts—the person cannot grow taller, but the bones can become thicker and the soft tissues can continue to grow
membranous bones, kyphosis
Possible role of decreased Growth hormone secretion in causing changes associated with aging
•
Therapy in older people : 1) increased protein deposition in the body, especially in the muscles; 2) decreased
fat deposits; 3) a feeling of increased energy
Posterior pituitary gland
(neurohypophysis)
• terminal nerve endings from
nerve tracts that originate in
the supraoptic and
paraventricular nuclei of the
hypothalamus
• endings lie on the surfaces of
capillaries, where they secrete
two posterior pituitary
hormones:
– 1) antidiuretic hormone (ADH),
also called vasopressin,
(supraoptic nuclei)
– 2) oxytocin (primarily in the
paraventricular nuclei)
Copyright: Hall, J. E., & Guyton, A. C. (2006). Guyton and Hall
textbook of medical physiology. Philadelphia, PA: Saunders
Elsevier.
Physiological functions of ADH
• ADH acts on the collecting ducts to increase
their permeability (aquaporins)
• Regulation of ADH production
– Osmotic regulation
• Osmoreceptors : the extracellular fluid becomes too
concentrated, fluid is pulled by osmosis out of the
osmoreceptor cell, decreasing its size and initiating
appropriate nerve signals in the hypothalamus to cause
additional ADH secretion
Physiological functions of ADH
• Regulation of ADH production
– Vasoconstrictor and pressor effects of ADH, and
increased ADH secretion caused by low blood
volume
• The stimuli for causing intense ADH secretion is
decreased blood volume
– The atria have stretch receptors that are excited by overfilling
(inhibition of ADH secretion)
• Decreased stretch of the baroreceptors of the carotid
aortic, and pulmonary regions (stimulation ADH
secretion)
Oxytocin hormone
• Oxytocin causes contraction of the pregnant
uterus
– stimulates contraction of the pregnant uterus,
especially toward the end of gestation
• Oxytocin aids in milk ejection by the breasts
– In lactation, oxytocin causes milk to be expressed
from the alveoli into the ducts of the breast
– Stimulus suckling stimulus on the nipple of the breast
- release of oxytocin by the posterior pituitary gland contraction of myoepithelial cells (milk letdown or
milk ejection)