The human glucagon receptor GCGR mediates the action of the pancreatic peptide hormone glucagon. Glucagon regulates blood glucose via control of hepatic glycogenolysis and gluconeogenesis and via regulation of insulin release from the beta cell. Type 2 diabetes is characterized by inappropriate regulation of hepatic glucose production, which is due to an imbalance in the bihormonal relationship between plasma levels of glucagon and insulin. The glucose-lowering effects of glucagon peptide antagonists and anti-glucagon antibodies have demonstrated the potential of glucagon receptor antagonism as a treatment for type 2 diabetes. Glucagon also elicits various effects in extrahepatic tissues, including adipose tissue, kidney, heart, pancreatic beta cells, gastrointestinal tract, thyroid and central nervous system.