GLUCAGON
Introduction
Glucagon is a peptide hormone secreted by the α-cells (alpha
cells) of the Islets of Langerhans of the pancreas. It is the chief hyperglycemic
hormone of the body and acts antagonistically to insulin. Its main function
is to increase blood glucose level during fasting and hypoglycemia. Glucagon:
- Mobilizes stored glucose
- Maintains blood glucose during
fasting
- Stimulates glycogen breakdown
- Stimulates glucose formation in
liver
Pancreas as an Endocrine Gland
The pancreas is both:
- Exocrine gland → secretes digestive enzymes
- Endocrine gland → secretes hormones
The endocrine part contains Islets of Langerhans.
Cells of Islets of Langerhans
|
Cell Type |
Hormone Secreted |
Main Function |
|
α-cells |
Glucagon |
Raises blood glucose |
|
β-cells |
Lowers blood glucose |
|
|
δ-cells |
Somatostatin |
Inhibitory hormone |
|
PP cells |
Pancreatic polypeptide |
GI regulation |
Chemical Nature of Glucagon
- Glucagon is a peptide hormone
- It consists of 29 amino acids
- It is derived
from a precursor called: Proglucagon
Synthesis of Glucagon
Steps
Step-1. Formation of Proglucagon
- Synthesized in α-cells
Step-2. Processing by Enzymes
- Processed by prohormone
convertase-2 (PC2)
Step-3. Formation of Glucagon
- Mature glucagon hormone released
Stimuli For Glucagon Secretion
Main Stimulus
Low Blood Glucose (Hypoglycemia)
Glucagon secretion increases during:
- Fasting
- Starvation
- Exercise
- Protein-rich meals
Factors Affecting Glucagon Secretion
Factors Increasing Secretion
- Hypoglycemia
- Amino acids
- Exercise
- Stress
- Sympathetic stimulation
Factors Decreasing Secretion
- Hyperglycemia
- Insulin
- Somatostatin
- GLP-1
Mechanism of Glucagon Secretion
When blood glucose falls:
↓ Blood glucose
↓
α-cells stimulated
↓
Glucagon secretion
↓
Liver stimulated
↓
Glucose released into blood
Mechanism of Action of Glucagon
Glucagon acts through a: G-protein coupled receptor (GPCR)
The receptor is mainly present in:
- Liver
- Adipose tissue
- Heart
- Kidney
Second Messenger System
Glucagon works through: cAMP pathway
Steps
- Glucagon binds receptor
- Adenyl cyclase activated
- cAMP formed
- Protein kinase activated
- Metabolic enzymes activated
Target Organs of Glucagon
Main target organ: Liver
Other targets: Adipose tissue, Heart
Functions of Glucagon
1. Effects on Carbohydrate Metabolism
Glucagon raises blood glucose level.
Major Actions
Breakdown of glycogen into glucose.
Formation of glucose from non-carbohydrate sources.
C. Inhibits Glycogenesis
Prevents storage of glucose as glycogen.
D. Inhibits Glycolysis
Decreases glucose breakdown in liver.
Overall Effect
↑ Blood glucose level
Therefore, glucagon is called: “Hyperglycemic Hormone”
2. Effects on Fat Metabolism
Glucagon promotes fat breakdown.
Actions
- Stimulates lipolysis
- Increases fatty acid oxidation
- Promotes ketogenesis
3. Effects on Protein Metabolism
- Promotes amino acid utilization
- Supports gluconeogenesis from
amino acids
4. Effects During Fasting
During fasting:
- Blood glucose falls
- Glucagon secretion rises
- Liver releases glucose
This maintains: Glucose homeostasis
Glucose Homeostasis
Blood glucose is controlled mainly by:
- Insulin
- Glucagon
After Meals
- Insulin predominates
- Glucose stored
During Fasting
- Glucagon predominates
- Glucose mobilized
Insulin vs Glucagon
|
Feature |
Insulin |
Glucagon |
|
Secreted by |
β-cells |
α-cells |
|
Blood glucose |
Decreases |
Increases |
|
Main action |
Glycogenesis |
Glycogenolysis |
|
Nature |
Hypoglycemic |
Hyperglycemic |
|
Fasting state |
Decreases |
Increases |
Glucagon in Starvation
During prolonged starvation:
- Glycogen stores depleted
- Glucagon stimulates
gluconeogenesis
- Fat metabolism increases
- Ketone bodies formed
Clinical Importance of Glucagon
1. Hypoglycemia
Glucagon is used therapeutically to treat: Severe hypoglycemia
Especially in: Diabetic patients receiving insulin
2. Diabetes Mellitus
In diabetes:
- Glucagon secretion may become
excessive
- Hyperglycemia worsens
3. Glucagonoma
Definition
Rare tumor of α-cells producing excess glucagon.
Features
- Hyperglycemia
- Weight loss
- Skin rash
- Diabetes mellitus
Glucagon and Exercise
During exercise:
- Muscles consume glucose
- Blood glucose may fall
- Glucagon secretion increases
- Liver releases glucose
Important Metabolic Effects
|
Process |
Effect of Glucagon |
|
Glycogenolysis |
Increased |
|
Gluconeogenesis |
Increased |
|
Glycogenesis |
Decreased |
|
Glycolysis |
Decreased |
|
Lipolysis |
Increased |
|
Ketogenesis |
Increased |
High-Yield Flowchart
Low Blood Glucose
↓
α-cells stimulated
↓
Glucagon secretion
↓
Liver glycogen breakdown
↓
Glucose released
↓
Increase in Blood Glucose
Important Facts
- Glucagon is secreted by α-cells
- It is a peptide hormone
- Contains 29 amino acids
- Raises blood glucose
- Acts mainly on liver
- Works via cAMP pathway
- Opposes insulin action
- Stimulates glycogenolysis and
gluconeogenesis
Point to Remember
“Glucagon is a peptide hormone, and plays an important role in
maintaining normal blood glucose levels.”
MEMORY TRICK
“GLUCAGON = GLUCOSE GONE UP”
Glucagon → Glucose ↑
Insulin → Glucose ↓
Quick Revision Table
|
Feature |
Glucagon |
|
Secreted by |
α-cells |
|
Nature |
Peptide hormone |
|
Amino acids |
29 |
|
Main target |
Liver |
|
Main action |
Raises blood glucose |
|
Mechanism |
cAMP pathway |
|
Opposes |
Insulin |
One-Line Summary
“Glucagon is a hyperglycemic peptide hormone secreted by pancreatic
α-cells that increases blood glucose mainly by stimulating glycogenolysis and
gluconeogenesis in the liver.”