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Glucagon
Dr. Sai Sailesh Kumar G
Professor
Department of Physiology
NRIIMS
Email: dr.goothy@gmail.com
Introduction
Glucagon, a hormone secreted by the alpha cells of the islets of
Langerhans when the blood glucose concentration falls
 Functions that are diametrically opposed to those of insulin
The most important of these functions is to increase the blood glucose
concentration
Introduction
Glucagon is a large polypeptide
It has a molecular weight of 3485
Composed of a chain of 29 amino acids
 Upon injection of purified glucagon into an animal, a profound hyperglycemic
effect occurs
Only 1 µg/kg of glucagon can elevate the blood glucose concentration by
approximately 20 mg/100 ml of blood (a 25 percent increase) in about 20 minutes
Introduction
Glucagon is also called the hyperglycemic hormone
Effects on glucose metabolism
The major effects of glucagon on glucose metabolism are
(1) breakdown of liver glycogen (glycogenolysis) and
(2) increased gluconeogenesis in the liver
greatly enhance the availability of glucose to the other organs of the
body
Glucagon Causes Glycogenolysis
The most dramatic effect of glucagon is its ability to cause
glycogenolysis in the liver, which in turn increases the blood glucose
concentration within minutes.
Glucagon Causes Glycogenolysis
1. Glucagon activates adenylyl cyclase in the hepatic cell membrane
2. Which causes the formation of cyclic adenosine monophosphate
3. Which activates protein kinase regulator protein
4. Which activates protein kinase
5. Which activates phosphorylase b kinase
6. Which converts phosphorylase b into phosphorylase a
7. Which promotes the degradation of glycogen into glucose-1-phosphate,
8. Which is then dephosphorylated, and the glucose is released from the liver cells.
Glucagon Causes Glycogenolysis
This sequence of events is exceedingly important for several reasons.
First, it is one of the most thoroughly studied of all the second
messenger functions of cyclic adenosine monophosphate.
Second, it demonstrates a cascade system in which each succeeding
product is produced in greater quantity than the preceding product.
Therefore, it represents a potent amplifying mechanism.
Glucagon Causes Glycogenolysis
 This mechanism explains how only a few micrograms of glucagon can
cause the blood glucose level to double or increase even more within a
few minutes.
Infusion of glucagon for about 4 hours can cause such intensive liver
glycogenolysis that all the liver stores of glycogen become depleted.
Glucagon Increases Gluconeogenesis
 Even after all the glycogen in the liver has been exhausted under the
influence of glucagon, continued infusion of this hormone still causes
continued hyperglycemia.
This hyperglycemia results from the effect of glucagon to increase the
rate of amino acid uptake by the liver cells
and then the conversion of many of the amino acids to glucose by
gluconeogenesis.
Glucagon Increases Gluconeogenesis
 This effect is achieved by activating multiple enzymes that are
required for amino acid transport and gluconeogenesis,
especially activation of the enzyme system for converting pyruvate to
phosphoenolpyruvate,
a rate-limiting step in gluconeogenesis.
Other effects of glucagon
 Most other effects of glucagon occur only when its concentration rises
well above the maximum normally in the blood.
 Perhaps the most important effect is that glucagon activates adipose
cell lipase, making increased quantities of fatty acids available to the
energy systems of the body.
Other effects of glucagon
 Glucagon also inhibits the storage of triglycerides in the liver
 Prevents the liver from removing fatty acids from the blood
this also helps make additional amounts of fatty acids available for the
other tissues of the body
Other effects of glucagon
 Glucagon in high concentrations also
(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
 The blood glucose concentration is by far the most potent factor that
controls glucagon secretion.
Note specifically, however, that the effect of blood glucose
concentration on glucagon secretion is in exactly the opposite direction
from the effect of glucose on insulin secretion
Regulation of glucagon secretion
 A decrease in the blood glucose concentration from its normal fasting
level of about 90 mg/100 ml of blood down to hypoglycemic levels can
increase the plasma concentration of glucagon severalfold.
 Conversely, increasing blood glucose to hyperglycemic levels
decreases the level of plasma glucagon
Regulation of glucagon secretion
 High concentrations of amino acids, the amino acids alanine and
arginine, stimulate the secretion of glucagon.
This is the same effect that amino acids have in stimulating insulin
secretion.
in this instance, the glucagon and insulin responses are not
opposites
Regulation of glucagon secretion
 During exhaustive exercise, the blood concentration of glucagon often increases
fourfold to fivefold.
The cause of this increase is not well understood
A beneficial effect of the glucagon is that it prevents a decrease in blood glucose.
One of the factors that might increase glucagon secretion during exercise is
increased circulating amino acids.
Other factors, such as β-adrenergic stimulation of the islets of Langerhans, may
also play a role
Somatostatin
 The delta cells of the islets of Langerhans secrete the hormone
somatostatin
14–amino acid polypeptide
 Extremely short half-life of only 3 minutes in the circulating blood.
Almost all factors related to the ingestion of food stimulate
somatostatin secretion.
Factors stimulating Somatostatin
 (1) increased blood glucose
(2) increased amino acids
(3) increased fatty acids
(4) increased concentrations of several of the gastrointestinal
hormones released from the upper gastrointestinal tract in response to
food intake
Inhibitory effects of Somatostatin
 1. Somatostatin acts locally within the islets of Langerhans
themselves to depress secretion of both insulin and glucagon
(Paracrine action).
2. Somatostatin decreases motility of the stomach, duodenum, and
gallbladder.
3. Somatostatin decreases both secretion and absorption in the
gastrointestinal tract.
Inhibitory effects of Somatostatin
Somatostatin depresses insulin and glucagon secretion
decreases utilization of the absorbed nutrients by the tissues
thus preventing rapid exhaustion of the food
and therefore making it available over a longer period
Inhibitory effects of Somatostatin
 somatostatin is the same chemical substance as growth hormone
inhibitory hormone, which is secreted in the hypothalamus and
suppresses the secretion of growth hormone by the anterior pituitary
gland
Diagnose?
 A 9-year-old child shows the following clinical features. Plumpness,
Immature facies, Small genitalia with delicate extremities. His body
proportions are according to his chronological age. What is the most
likely cause of all these features?
Diagnose?
 A person visited his family physician with complains that he is
constantly thirsty and in the bathroom day and night relieving his
bladder. The doctor advised blood and urine tests to check his normal
glucose levels which were normal. What do you think this person is
suffering from?
Diagnose?
 An expectant mother has started taking alcohol in moderation to
overcome emotional stress and psychic factors. The secretion of which
pituitary hormone would be affected? How it may affect the child birth
and her subsequent relationship with the child.
Diagnose?
 A 20-year-old male was admitted to the medical ward with weight loss
despite excessive eating. On clinical examination, the only findings are
anxious looks, slightly dehydrated, and there is a non-heling ulcer on
the left foot from the last 25 days. Give the diagnosis. How will you
confirm it?
Diagnose?
Mr. Sharma, 47-years obese man attends your OPD with a compliant
of tingling sensation in fingers. He has observed that he has an
increased frequency of micturition and he feels thirsty all the time. Of
late, he has an urge to eat more and more. The family history of type-2
DM present in the father and maternal grand mother. He has been on
antihypertensive medication since 4 years.
THANK YOU

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Glucagon-9.pptx- Physiology, functions, regulation

  • 1. Glucagon Dr. Sai Sailesh Kumar G Professor Department of Physiology NRIIMS Email: dr.goothy@gmail.com
  • 2. Introduction Glucagon, a hormone secreted by the alpha cells of the islets of Langerhans when the blood glucose concentration falls  Functions that are diametrically opposed to those of insulin The most important of these functions is to increase the blood glucose concentration
  • 3. Introduction Glucagon is a large polypeptide It has a molecular weight of 3485 Composed of a chain of 29 amino acids  Upon injection of purified glucagon into an animal, a profound hyperglycemic effect occurs Only 1 µg/kg of glucagon can elevate the blood glucose concentration by approximately 20 mg/100 ml of blood (a 25 percent increase) in about 20 minutes
  • 4. Introduction Glucagon is also called the hyperglycemic hormone
  • 5. Effects on glucose metabolism The major effects of glucagon on glucose metabolism are (1) breakdown of liver glycogen (glycogenolysis) and (2) increased gluconeogenesis in the liver greatly enhance the availability of glucose to the other organs of the body
  • 6. Glucagon Causes Glycogenolysis The most dramatic effect of glucagon is its ability to cause glycogenolysis in the liver, which in turn increases the blood glucose concentration within minutes.
  • 7. Glucagon Causes Glycogenolysis 1. Glucagon activates adenylyl cyclase in the hepatic cell membrane 2. Which causes the formation of cyclic adenosine monophosphate 3. Which activates protein kinase regulator protein 4. Which activates protein kinase 5. Which activates phosphorylase b kinase 6. Which converts phosphorylase b into phosphorylase a 7. Which promotes the degradation of glycogen into glucose-1-phosphate, 8. Which is then dephosphorylated, and the glucose is released from the liver cells.
  • 8. Glucagon Causes Glycogenolysis This sequence of events is exceedingly important for several reasons. First, it is one of the most thoroughly studied of all the second messenger functions of cyclic adenosine monophosphate. Second, it demonstrates a cascade system in which each succeeding product is produced in greater quantity than the preceding product. Therefore, it represents a potent amplifying mechanism.
  • 9. Glucagon Causes Glycogenolysis  This mechanism explains how only a few micrograms of glucagon can cause the blood glucose level to double or increase even more within a few minutes. Infusion of glucagon for about 4 hours can cause such intensive liver glycogenolysis that all the liver stores of glycogen become depleted.
  • 10. Glucagon Increases Gluconeogenesis  Even after all the glycogen in the liver has been exhausted under the influence of glucagon, continued infusion of this hormone still causes continued hyperglycemia. This hyperglycemia results from the effect of glucagon to increase the rate of amino acid uptake by the liver cells and then the conversion of many of the amino acids to glucose by gluconeogenesis.
  • 11. Glucagon Increases Gluconeogenesis  This effect is achieved by activating multiple enzymes that are required for amino acid transport and gluconeogenesis, especially activation of the enzyme system for converting pyruvate to phosphoenolpyruvate, a rate-limiting step in gluconeogenesis.
  • 12. Other effects of glucagon  Most other effects of glucagon occur only when its concentration rises well above the maximum normally in the blood.  Perhaps the most important effect is that glucagon activates adipose cell lipase, making increased quantities of fatty acids available to the energy systems of the body.
  • 13. Other effects of glucagon  Glucagon also inhibits the storage of triglycerides in the liver  Prevents the liver from removing fatty acids from the blood this also helps make additional amounts of fatty acids available for the other tissues of the body
  • 14. Other effects of glucagon  Glucagon in high concentrations also (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
  • 15. Regulation of glucagon secretion  The blood glucose concentration is by far the most potent factor that controls glucagon secretion. Note specifically, however, that the effect of blood glucose concentration on glucagon secretion is in exactly the opposite direction from the effect of glucose on insulin secretion
  • 16.
  • 17. Regulation of glucagon secretion  A decrease in the blood glucose concentration from its normal fasting level of about 90 mg/100 ml of blood down to hypoglycemic levels can increase the plasma concentration of glucagon severalfold.  Conversely, increasing blood glucose to hyperglycemic levels decreases the level of plasma glucagon
  • 18. Regulation of glucagon secretion  High concentrations of amino acids, the amino acids alanine and arginine, stimulate the secretion of glucagon. This is the same effect that amino acids have in stimulating insulin secretion. in this instance, the glucagon and insulin responses are not opposites
  • 19. Regulation of glucagon secretion  During exhaustive exercise, the blood concentration of glucagon often increases fourfold to fivefold. The cause of this increase is not well understood A beneficial effect of the glucagon is that it prevents a decrease in blood glucose. One of the factors that might increase glucagon secretion during exercise is increased circulating amino acids. Other factors, such as β-adrenergic stimulation of the islets of Langerhans, may also play a role
  • 20. Somatostatin  The delta cells of the islets of Langerhans secrete the hormone somatostatin 14–amino acid polypeptide  Extremely short half-life of only 3 minutes in the circulating blood. Almost all factors related to the ingestion of food stimulate somatostatin secretion.
  • 21. Factors stimulating Somatostatin  (1) increased blood glucose (2) increased amino acids (3) increased fatty acids (4) increased concentrations of several of the gastrointestinal hormones released from the upper gastrointestinal tract in response to food intake
  • 22. Inhibitory effects of Somatostatin  1. Somatostatin acts locally within the islets of Langerhans themselves to depress secretion of both insulin and glucagon (Paracrine action). 2. Somatostatin decreases motility of the stomach, duodenum, and gallbladder. 3. Somatostatin decreases both secretion and absorption in the gastrointestinal tract.
  • 23. Inhibitory effects of Somatostatin Somatostatin depresses insulin and glucagon secretion decreases utilization of the absorbed nutrients by the tissues thus preventing rapid exhaustion of the food and therefore making it available over a longer period
  • 24. Inhibitory effects of Somatostatin  somatostatin is the same chemical substance as growth hormone inhibitory hormone, which is secreted in the hypothalamus and suppresses the secretion of growth hormone by the anterior pituitary gland
  • 25. Diagnose?  A 9-year-old child shows the following clinical features. Plumpness, Immature facies, Small genitalia with delicate extremities. His body proportions are according to his chronological age. What is the most likely cause of all these features?
  • 26. Diagnose?  A person visited his family physician with complains that he is constantly thirsty and in the bathroom day and night relieving his bladder. The doctor advised blood and urine tests to check his normal glucose levels which were normal. What do you think this person is suffering from?
  • 27. Diagnose?  An expectant mother has started taking alcohol in moderation to overcome emotional stress and psychic factors. The secretion of which pituitary hormone would be affected? How it may affect the child birth and her subsequent relationship with the child.
  • 28. Diagnose?  A 20-year-old male was admitted to the medical ward with weight loss despite excessive eating. On clinical examination, the only findings are anxious looks, slightly dehydrated, and there is a non-heling ulcer on the left foot from the last 25 days. Give the diagnosis. How will you confirm it?
  • 29. Diagnose? Mr. Sharma, 47-years obese man attends your OPD with a compliant of tingling sensation in fingers. He has observed that he has an increased frequency of micturition and he feels thirsty all the time. Of late, he has an urge to eat more and more. The family history of type-2 DM present in the father and maternal grand mother. He has been on antihypertensive medication since 4 years.