1. Glucagon – A hormone from pancreas Lecture NO:1st BDS
Dr Muhammad Ramzan

2. Glucagon – the definition hyperglycemic agent
A peptide hormone secreted by the α - cells of the islets of Langerhans in response to hypoglycemia
It increases plasma glucose level, opposite to the action of Insulin by ↑ hepatic Glycogenolysis

3. Glucagon – the back ground
Both, Insulin ad Glucagon play a central role in glucose homeostasis mg/dl
Glucagon induces the liver/ other tissues to deliver glucose through: Glycogenolysis and Gluconeogenesis
It is a major player in providing glucose to the brain in hypoglycemia - the only nutrient for the neurons and RBC

4. Glucose Homeostasis – Insulin/ Glucagon

5. Glucagon – the Target tissue - 2 No receptors for muscles
These are the tissues with Glucagon receptors
Hepatocytes and Adipocytes
Muscles have no receptors for Glucagon and do not contribute in ↑blood glucose level in hypoglycemia

6. Glucagon – the biosynthesis 2 sources
There are 2 sources for Glucagon synthesis
α – cells in Islets of Langerhans
L- Cells – Intestinal mucosal cells

7. Glucagon – the biosynthesis 1 α – Islets cells
Glucagon is secreted as a Prohormone having 160 AAs in RER of α - Islet cells
It is cleaved in the RER of α - cells to 4 peptides including 29 Amino acids Glucagon
Is packed in Golgi complex and stored as secretary vesicles in α- cell cytoplasm
It is released in response to a stimulus - Hypoglycemia

8. Glucagon – Biosynthesis in L- Cells

9. Glucagon – the biosynthesis 2 L- cells in intestinal mucosa
Glucagon is also secreted in the L- cells of small intestine
These are mucosal cells with granules of hormones such as Glucagon - like peptide 1
Processing results in the formation of different glucagon like peptides, some with physiological importance

10. Glucagon – the structure

11. Glucagon – regulation of secretion hypoglycemia is major stimulator
Regulation of Glucagon secretion is complex and depends upon fed/fasting state and nutrients like :
CHOs (glucose, Ketone) ; Lipids,(FA) and Proteins (AA)
Hormones levels and interaction - Insulin and Glucagon
Autonomic nervous system
Physical factors :trauma,surgary and infections
Some may stimulate, while others suppress its secretion

12. Glucagon secretion – the stimulators Hypoglycemia ≤ 70mg/dl – the major one
Hypoglycemia: Fasting/starvation, exercise and period B/W the diet
Diet : protein rich diet – AAs (Leucine)
Hormones: GIT hormones like Gastrin and Cholicystokinin
Neurotransmitters like Catecholamine and Acetylcholine
Parasympathetic Nervous System

13. Glucagon secretion – the inhibitors Hyperglycemia and Insulin
Diet : CHO and fat rich diet including:
Glucose, Ketone and fatty acids
Hyperglycemia (≥ 160mg/dl
Hormones like Insulin

14. Glucagon – the mechanism of action GPCR
Glucagon is a protein hormone with the action similar to the rest of the ones
Glucagon binds to its receptor/ GPCR and produces
conformation changes in the membranous portion
This activates Cytoplasmic G proteins which has α, β, and γ subunits in theI slet α – cell

15. Glucagon – The mechanism of action Activation G - Protein and enzyme
It results in the replacement of the α -GDP molecule that with a α-GTP molecule.
This substitution causes the release of α - subunit from the β and γ subunits.
The α GTP subunit activates the membranous enzyme Adenylate Cyclase.

16. GPRC activation

17. Glucagon– mechanism of action Formation of c - AMP
Adenylate Cyclase produces c AMP from ATP which
activates cAMP dependent protein kinase A
It Phosphorylates activates no of proteins/enzymes including Glycogen Phosphorylase converting it to Phosphorylase A
An enzyme responsible for the release of Glucose – 1- phosphate from Glycogen to↑ blood glucose level

18. Glucagon – the metabolic role on CHO, fats and proteins
The major role of Glucagon is on glucose metabolism
Glucagon ↑ blood glucose level when it is too low
hypoglycemia - ≤ 70mg/dl and to maintain it at :
normal level mg/dl
It has got minor effect on fat metabolism
With no significant action on protein metabolism

19. Glucagon – major metabolic role Liver is the key player

20. Glucagon - Effects on CHO metabolism Glycogenolysis
In hypoglycemia, Glucagon stimulates hepatic Glycogenolysis and glucose is released to ↑ its level
It inhibits hepatic Glycogenesis by inhibiting hepatic Glycogen Synthase
It stimulate Gluneogenesis – a process of converting amino acids to glucose

21. Glucagon- Glycogenolysis

22. Glucagon – effects on CHO metabolism Liver is a major shareholder

23. Glucagon - Effects on lipid metabolism Lipolysis – β oxidation and Ketogenesis
Glucagon has got minor effects on fat metabolism
It ↑ Lipolysis and serum fatty acid level by releasing TG from the adipose tissues
It ↑ β oxidation of FAs and hepatic Ketogenesis to conserve glucose in hypoglycemia
It reduces Lipogenesis

24. Glucagon - Effects on protein metabolism promotes Gluconeogenesis
Glucagon promotes Proteolysis (of skeletal muscles) and releases AAs into the circulation
The free AAs are not used for Proteogenesis but for hepatic Gluconeogenesis
This serves to ↑the blood glucose level through the action of Glucagon to relieve hypoglycemia

25. Glucagon - secretion abnormalities Deficiency - Hypoglycemia
Diseases associated with high or low secretion of Glucagon are rare
Excess of Glucagon is due to α – cell hyperplasia and carcinoma that leads to wasting syndrome
Glucagon deficiency produces low hepatic glucose production and fasting hypoglycemia

26. Comparison B/W Insulin and Glucagon