Glucagon
Glucagon is a 29-amino-acid peptide hormone secreted by alpha cells (α-cells) of the pancreatic islets of Langerhans. It is the principal counter-regulatory hormone to insulin, with the primary function of raising blood glucose levels.
Glucose homeostasis: the antagonistic interplay between insulin (lowers glucose) and glucagon (raises glucose)
Core Mechanism: Raising Blood Glucose
When blood glucose falls (fasting, exercise, hypoglycemia), alpha cells release glucagon. It acts primarily on the liver (hepatocytes) via Gs-coupled glucagon receptors → cAMP → PKA activation:
- Glycogenolysis — breakdown of stored glycogen → glucose-1-phosphate → blood glucose. Fast response (minutes).
- Gluconeogenesis — synthesis of new glucose from amino acids (alanine, glutamine), lactate, and glycerol. Slower but sustained.
- Ketogenesis — in prolonged fasting, promotes fatty acid oxidation and ketone body production as alternative fuel for the brain.
Glucagon also has minor effects on muscle and adipose tissue, but hepatic action dominates.
Counter-Regulatory Response to Hypoglycemia
The counter-regulatory response is the body’s defense against low blood glucose:
| Hormone | Source | Action |
|---|---|---|
| Glucagon | Pancreatic α-cells | ↑ glycogenolysis, ↑ gluconeogenesis |
| Epinephrine | Adrenal medulla | ↑ glycogenolysis, ↑ lipolysis, ↑ glucagon secretion |
| Cortisol | Adrenal cortex | ↑ gluconeogenesis (slower) |
| GH | Anterior pituitary | ↑ lipolysis, insulin resistance |
Glucagon is the fastest and most specific counter-regulatory hormone. In type 1 diabetes, the glucagon response to hypoglycemia is often blunted, increasing hypoglycemia risk.
Insulin–Glucagon Axis
Insulin and glucagon are antagonists that maintain glucose within ~70–110 mg/dL:
- Postprandial (fed state): High insulin suppresses glucagon → glucose uptake and glycogen storage
- Fasted state: Low insulin, high glucagon → hepatic glucose output
- The insulin:glucagon ratio (rather than absolute levels) governs net hepatic glucose metabolism
Glucagon secretion is inhibited by: glucose, insulin, somatostatin (from δ-cells). It is stimulated by: amino acids (especially arginine), β-adrenergic signals, cortisol.
Role in Exercise
During sustained exercise, glucagon rises and insulin falls, maintaining glucose supply to working muscles. Hepatic glucose output increases ~3–5× to match demand.
Clinical Use
- Glucagon emergency kit: Injectable glucagon (or intranasal powder) for severe hypoglycemia when the patient is unconscious and cannot take oral glucose. Raises blood glucose within 10–15 minutes.
- GLP-1 analogs (e.g., semaglutide): Mimic GLP-1, which suppresses glucagon; major mechanism in type 2 diabetes treatment and weight loss drugs.
- Glucagon stimulation test: Used to assess growth hormone reserve and insulin secretory capacity.
see also
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Erstellt: 01-09-22 11:13