Glucagon Receptor

Glucagon is a 29-amino acid polypeptide secreted by the alpha or glucagon cell of the islet of Langerhans in response to hypoglycemia, arginine, gastric inhibitory polypeptide (during ambient reduced glucose levels), gastrin, and potassium chloride. Glucagon action is transduced by a G-protein-coupled receptor (GCGR/Gcgr) that is a member of the class II GCGR superfamily of seven transmembrane spanning receptors that are coupled via GTP-binding proteins to adenyl cyclase resulting in an increase in cAMP production. cAMP activates signaling pathways that cause an increase in gluconeogenesis, glycogenolysis, and fatty acid oxidation. In addition, glucagon controls glucose, energy, and lipid metabolism at least in part via AC/cAMP independent signals including p38MAPK, IP3/DAG/Ca, peroxisome proliferator-activated receptor-α (PPARα) and fibroblast growth factor 21 (FGF21)-dependent pathways. Binding sites for glucagon have been identified in liver, kidney, intestinal smooth muscle, brain, adipose tissue, heart, pancreatic islet beta cells and placenta.  Gcgr expression is positively regulated by glucose and negatively regulated by glucagon and agents that increase intracellular cAMP.

1.Charron MJ,et al. J Endocrinol. 2015;224(3):R123–R130.