GLUCAGON- exam ready notes

 

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	Insulin	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

1. Glucagon binds receptor
2. Adenyl cyclase activated
3. cAMP formed
4. Protein kinase activated
5. 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

A. Glycogenolysis

Breakdown of glycogen into glucose.

B. Gluconeogenesis

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.”