Glucagon

Glucagon is a 29-amino-acid peptide hormone secreted by pancreatic alpha-cells in response to hypoglycemia, prolonged fasting, and amino acid ingestion, and suppressed by glucose and insulin. It acts on hepatic glucagon receptors to stimulate glycogenolysis and gluconeogenesis, raising blood glucose, and promotes hepatic ketogenesis during fasting. It is classically viewed as the counter-regulatory hormone to insulin, and the glucagon-to-insulin ratio is an important determinant of hepatic fuel partitioning. In type 2 diabetes, glucagon secretion is paradoxically elevated postprandially and resistant to glucose-mediated suppression, contributing to hyperglycemia; GLP-1 receptor agonists partly correct this by potentiating insulin and suppressing inappropriate glucagon release. Newer dual and triple agonists targeting glucagon, GLP-1, and GIP receptors are in clinical development for obesity and metabolic disease.