Glucagon

Glucagon is a 29-amino-acid peptide hormone produced and secreted mainly by alpha cells in the pancreatic islets. It is an important regulator of blood glucose, particularly when glucose availability is low. Low blood glucose is an important stimulus for glucagon secretion, while amino acids, neural signals, and hormones produced within and outside the pancreatic islets also influence its release .^1,2

Glucagon acts primarily on the liver. It binds to the glucagon receptor, a G protein-coupled receptor on hepatocytes, and activates intracellular signaling that prominently involves cyclic AMP and protein kinase A. These signals alter the activity and expression of metabolic enzymes, allowing the liver to adjust its production and use of metabolic fuels .²

A major effect of glucagon is to increase hepatic glucose output. It stimulates glycogenolysis, the breakdown of stored liver glycogen, and promotes gluconeogenesis, the production of glucose from noncarbohydrate precursors. Glucagon also influences hepatic amino-acid and lipid metabolism, particularly during fasting and other conditions in which nutrient supply is limited .^1,2

Glucagon and insulin have complementary and often opposing effects on glucose metabolism. Insulin favors glucose use and storage when nutrients are abundant, whereas glucagon promotes hepatic glucose mobilization and production when glucose availability is low. Glucagon therefore functions as an important counter-regulatory hormone to insulin, although both hormones participate in a coordinated system for maintaining metabolic homeostasis .^1,2