glucagon

Glucagon is a peptide hormone produced by the alpha cells of the pancreatic islets. It consists of 29 amino acids and is encoded by the GCG gene. In the pancreas, glucagon is synthesized as part of the larger proglucagon precursor, which is proteolytically processed to yield the active hormone. Related proglucagon-derived peptides are also produced in other tissues.

Glucagon acts mainly on the liver via the glucagon receptor, a Gs-coupled receptor. Binding increases intracellular cyclic AMP, activating protein kinase A. This signaling promotes glycogenolysis and gluconeogenesis, increasing hepatic glucose output. It also stimulates lipolysis and ketogenesis in adipose tissue and supports energy production during fasting.

Secretion is primarily stimulated by low blood glucose and elevated amino acids, and is inhibited by high glucose and insulin. Sympathetic activation and gut-derived factors can influence release. In the post-absorptive state, glucagon helps maintain blood glucose between meals and during fasting, complementing insulin’s actions to regulate carbohydrate metabolism.

Clinically, recombinant glucagon is used to treat severe hypoglycemia, especially in diabetic patients, when oral glucose cannot be given or absorbed. It is administered by intramuscular, subcutaneous, or intravenous injection. In diagnostic radiology and gastroenterology, glucagon may be used to relax the GI tract to reduce motility during imaging procedures.

Glucagon also has extrahepatic roles in metabolism and is studied for effects on appetite and energy balance. Adverse effects are generally mild but may include nausea and vomiting. The hormone’s actions are counterbalanced by insulin and other hormones to maintain glucose homeostasis.