Glucagon
A 29-amino-acid peptide from islet α cells that raises blood glucose during fasting by stimulating hepatic glycogenolysis, gluconeogenesis and ketogenesis — the main counter-regulatory hormone to insulin.
Overview
Glucagon is cleaved from proglucagon by prohormone convertase 2 in α cells (in intestinal L cells the same precursor yields GLP-1, GLP-2 and oxyntomodulin instead). It acts mainly on the liver, where the glucagon receptor (Gs) raises cAMP and activates PKA: glycogen phosphorylase is activated and glycogen synthase inhibited (glycogenolysis), gluconeogenic enzymes (PEPCK, fructose-1,6-bisphosphatase) are induced and fructose-2,6-bisphosphate falls (gluconeogenesis), and malonyl-CoA falls, relieving inhibition of carnitine palmitoyltransferase-1 so that fatty acids enter mitochondria for β-oxidation and ketogenesis. It also increases hepatic amino-acid uptake and ureagenesis.
The insulin:glucagon ratio in portal blood determines whether the liver stores or releases fuel. After a protein meal both rise — glucagon prevents the hypoglycaemia that amino-acid-stimulated insulin would otherwise cause.
- Location
Source: α cells of the pancreatic islets. Targets: liver (main), kidney, adipose tissue, heart.
Function
- Raises blood glucose by glycogenolysis and gluconeogenesis.
- Promotes hepatic fatty-acid oxidation and ketone body production.
- Increases hepatic amino-acid uptake and urea production.
- Physiology
Class: peptide (29 aa). Receptor: glucagon receptor — Gs/cAMP. Half-life ≈5–6 min (largely cleared by liver and kidney).
- Regulation
Stimulated by hypoglycaemia, amino acids (especially arginine, alanine), sympathetic activity and epinephrine (β2), exercise, stress and cortisol. Inhibited by glucose, insulin (paracrine), somatostatin, GLP-1 and free fatty acids.
Clinical significance
Glucagon for severe hypoglycaemia
IM/SC or nasal glucagon restores glucose in an unconscious patient, but only if hepatic glycogen is available (ineffective in starvation or alcohol-related hypoglycaemia).
β-blocker and calcium-channel blocker overdose
High-dose glucagon raises myocardial cAMP independently of β receptors, increasing heart rate and contractility.
Glucagonoma
α-cell tumour: necrolytic migratory erythema, diabetes, weight loss, stomatitis, deep vein thrombosis and depression.
Compiled from standard anatomy and physiology references — see the Endocrine System sources. For education only; not medical advice.