A peptide hormone secreted by pancreatic alpha cells that raises blood glucose levels, functioning as a crucial counterregulatory hormone to insulin in maintaining blood sugar homeostasis.

Glucagon

Glucagon is a fundamental hormone in metabolic regulation, produced by the alpha cells of the pancreatic islets in response to low blood glucose levels. This 29-amino acid peptide plays a central role in glucose homeostasis, acting as the primary counterbalance to insulin.

Synthesis and Structure

The hormone is synthesized as a larger precursor molecule called proglucagon, which undergoes tissue-specific processing:

In pancreatic α-cells: produces glucagon
In intestinal L-cells: produces GLP-1 and GLP-2

Physiological Actions

Primary Functions

Hepatic Glucose Production
- Stimulates glycogenolysis (breakdown of glycogen)
- Enhances gluconeogenesis (glucose synthesis)
- Inhibits glycolysis (glucose breakdown)
Lipid Metabolism
- Promotes lipolysis in adipose tissue
- Increases fatty acid oxidation
- Stimulates ketogenesis during prolonged fasting

Metabolic Effects

Raises blood glucose levels
Increases energy expenditure
Promotes protein catabolism
Enhances cardiac contractility

Regulation

Glucagon secretion is controlled by multiple factors:

Stimulated by:
- Low blood glucose
- Amino acids
- Sympathetic nervous system activation
Inhibited by:
- High blood glucose
- Insulin
- Somatostatin

Clinical Significance

Disorders

Diabetes Mellitus: Inappropriate glucagon secretion contributes to hyperglycemia
Glucagonoma: Rare pancreatic tumor producing excess glucagon

Therapeutic Applications

Treatment of severe hypoglycemia
Management of beta blocker overdose
Diagnostic testing in endocrinology

Research Directions

Current areas of investigation include:

Development of glucagon receptor antagonists
Role in metabolic syndrome
Potential therapeutic applications beyond hypoglycemia
Integration with artificial pancreas systems

Interactions with Other Hormones

Glucagon functions within a complex network of metabolic hormones:

Insulin (primary antagonist)
Epinephrine (synergistic effects)
Growth Hormone (indirect interactions)

Understanding glucagon's role in metabolism continues to reveal new therapeutic targets for metabolic disorders and diabetes management.