Glucagon is a peptide hormone produced by pancreatic alpha cells that plays a crucial role in glucose metabolism by opposing the action of insulin. It stimulates glycogenolysis and gluconeogenesis in the liver while promoting lipolysis and amino acid transport, helping to maintain blood glucose levels, especially during fasting or stress. Glucagon's secretion is regulated by factors such as low blood glucose, amino acids, and stress hormones, while it serves to prevent hypoglycemia between meals.

1. Glucagon
Dr. Rupali A. Patil
Associate Professor, Pharmacology Department
GES’s Sir Dr. M. S. Gosavi College of Pharmaceutical
Education & Research, Nashik

2. GLUCAGON
• Peptide hormone secreted by pancreatic alpha cells.
• Glucagon is a polypeptide (29 amino acid) with a molecular weight of 3500.
• Counterregulatory hormone: opposes insulin action.
• Other counter-regulatory hormones: epinephrine, norepinephrine, cortisol, GH.
• Binds G-protein coupled receptors in specific tissues (i.e. liver).

3. GLUCAGON SECRETION
Pancreatic alpha cell
• Glucagon: single polypeptide chain
• Pre-proglucagon: cleaved to produce
diff. products in diff. tissues (i.e. intestinal GLP-1)
• Pre-proglucagon --> --> --> glucagon
 Stored in dense granules
 Released by Exocytosis.
 Ca is needed for exocytosis.

4. PLASMA LEVELS
 Circulating Glucagon – Unbound.
 Basal level in Fasting – 100-150 pg/ml.
 Half life – 6 min (5-9 min)
 Secretion Rate 100 -150 μg/day.
 Degradation – in liver & kidney

5. Activate secretion:
• Low blood glucose (primary stimulus)
• Stress hormones: (nor)epinephrine override alpha cell's response during
physiologic stress
• Amino acids: high protein meal stimulates glucagon secretion (counters insulin
secretion)
• Gi hormones (cck, gastrin)
• Cortisol, growth hormone
• Exercise
• Infections
•  Adrenergic stimulus, ACh

6. Inhibitors
 Elevated plasma [glucose]
 Somatostatin
 Secretin
 FFA, ketones
 Insulin
-Adrnergic stimulation, GABA

7. Regulation of secretion
 Role of blood levels of
Nutrients.
 Blood Glucose level – BSL
• >70mg% stimulate
 Plasma amino acids-
protein rich meal
specially Arginine &
Alanine.
 Free fatty acids & keto-
acids – Negative feedback
relationship.
 Role of GIT hormones –
CCK-PZ, Gastrin, GIP
stimulates
 Role of Nervous system
–sympathetic nerve
stimulation – increases
 Stress, fasting, exercise,
infection – increases
 Vagal stimulation,
acetylcholine – increases.

8. Mechanism of action

9. ACTIONSOFGLUCAGON
 Mobilization of storednutrients
• Glucose, fatty acids, ketoacids.
 Action exactly opposite to insulin.
 Hormone of energy release.

10. ACTIONSOF GLUCAGON
 Carbohydrate metabolism
 Protein metabolism
 Fat metabolism
 Other actions

11. Actions
• Hepatocytes: receptors for glucagon and epinephrine
• Counter regulatory hormones control same processes, but respond to other
stimuli (i.e. stress)
• Muscle cells: only receptors for epinephrine NOT glucagon
1. Binds G-protein coupled receptor on hepatic cell
2. Alpha subunit exchanges GDP for GTP
3. Alpha subunit activates adenylyl cylase, which activates PKA
4. PKA phosphorylates downstream enzymes
5. Activates glycogen & lipid breakdown, and gluconeogenesis
6. Inhibits glycogen, protein and lipid synthesis
Long-term response: increases transcription of gluconeogenic enzymes (~hrs/days)

12. Effect on glucose levels

13. Carbohydrate metabolism
 Glycogen: Increases glycogenolysis in liver &
not in muscle
 Glucose-1-Phosphate (inhibit Glycogen synthetase)
 Glucose: Increases gluconeogenesis in liver.
Formation of Glucose from Lactate, Pyruvate,
Glycerol & amino acids.

14. Fat metabolism
 Increases lipolysis – excess FFA oxidized – energy production -
ketogenesis in liver.
 Increases release of FFA & Glycerol from adipose tissue and makes it
available for peripheral utilization.
 Prevents synthesis of triglycerides
 Thus Glucagon – Ketogenic & Hyperglycemic Hormone.

15. Protein metabolism
 Increases Gluconeogenesis by increasing transport of Amino Acids into liver.
 Lowers plasma amino acids.
 CALORIGENIC EFFECT
• Due to increased hepatic deamination of amino acids

17. Other actions
 Inhibit renal tubular Na reabsorption –
• Natriuresis.
 Increases Cardiac force of contraction – activation of myocardial Adenyl cyclase.
 Stimulate secretion of growth hormone, insulin & Somatostatin
 Regulation of appetite.
 Increases secretion of bile.
 Inhibits secretion of gastric juice.

18. Pancreatic hormones, insulin & glucagon regulate
metabolism

19. Actions

20. CLINICAL CORRELATION
• Hypoglycaemia
• Acute drop in blood glucose levels to below 60 mg/dL
• Symptoms range from dizziness to coma and even death
• Brain and red blood cells depend on glucose for energy

21. PREVENTIONOF OCCURRENCE OF HYPERGLYCEMIA
 Hyperglycemia after a carbohydrate meal or mixed meal is
prevented by 4-5 times increase in INSULIN secretion.
 Increase uptake & utilization as chief fuel
 Promotes store of glucose as glycogen in liver & TG in adipose tissue.
 Inhibit Gluconeogenesis & Glycogenolysis.

22. PREVENTIONOF OCCURRENCE OF HYPERGLYCEMIA…..
• There is only one hormone to prevent Hyperglycemia – Insulin
• But 4 hormones to prevent Hypoglycemia
• Glycogen, Growth hormone, Glucocorticoids & Epinephrine.
• Organs cannot use any fuel other than glucose so vulnerable to
Hypoglycemia are –
Brain, Retina & Germinal Epithelium of gonads

23. PREVENTIONOF OCCURRENCE OF HYPERGLYCEMIA
 Role of Glucagon – prevent hypoglycemia between meals (few hours).
 Promotes Glycogenolysis & Gluconeogenesis.
 Lipolysis in adipose tissue& use FFA as chief fuel.
 Role of Epinephrine (Many hours) – stimulate sympathetic nervous
system through Hypothalamus
 Supplement actions of Glycogen
 Increase FFA production by lipolysis.
 Role of growth hormones & Glucocorticoids(Few days) – decrease
peripheral use of Glucose.

24. THANKYOU …….