Glucagon

Glucagon is a 29-amino acid peptide hormone produced by pancreatic alpha cells and is the principal counterregulatory hormone to insulin. FDA-approved since 1960 under the brand GlucaGen, it is the standard emergency treatment for severe hypoglycemia. It also serves as a diagnostic aid in gastrointestinal imaging. Endogenous glucagon is essential for hepatic glucose mobilization during fasting.

Glucagon binds the glucagon receptor (GCGR), a class B GPCR expressed predominantly in the liver. Receptor activation stimulates adenylate cyclase, raising intracellular cAMP and activating protein kinase A (PKA), which triggers glycogenolysis (glycogen breakdown) and gluconeogenesis (de novo glucose synthesis), rapidly raising blood glucose. In pharmacological use, it reverses insulin-induced hypoglycemia within minutes. It also relaxes GI smooth muscle, making it useful as a contrast aid during endoscopy and imaging.

Glucagon has an extensively documented clinical record spanning 60+ years. GlucaGen (Novo Nordisk) and Baqsimi (nasal powder) are FDA-approved formulations. Research is exploring glucagon dual agonism alongside GLP-1 for obesity treatment. Cotadutide and other GLP-1/glucagon co-agonists are in Phase 2–3 trials for NASH and metabolic disease. Glucagon excess (hyperglucagonemia) is increasingly recognized as a driver of type 2 diabetes pathophysiology.