Human glucagon receptor (GCGR)

The human glucagon receptor (GCGR) is a class B G protein-coupled receptor (GPCR) that is primarily responsible for mediating the effects of the peptide hormone glucagon, which is secreted by pancreatic alpha cells during fasting or hypoglycemic states. GCGR is highly expressed in the liver, where it regulates glucose homeostasis—upon glucagon binding, the receptor activates intracellular signaling cascades resulting in the mobilization and release of glucose into the bloodstream. GCGR couples predominantly to Gs proteins, stimulating adenylate cyclase and raising intracellular cyclic AMP (cAMP), and to a lesser extent couples to Gi and Gq, engaging multiple secondary messenger pathways including phospholipase C activation and calcium signaling. Structurally, GCGR features an extracellular domain connected via a stalk to a seven transmembrane (7TM) helical domain; both domains are essential for ligand recognition and signaling. The receptor is considered an important therapeutic target for metabolic diseases, particularly type 2 diabetes, and has been the subject of investigations into receptor antagonists that could reduce hepatic glucose production. Pathogenic mutations in the GCGR gene can lead to glucagon resistance, hyperglucagonemia, and pancreatic neuroendocrine tumors, underscoring its relevance in both normal physiology and disease.

Other names

Glucagon receptorGCGRGlucagon G protein-coupled receptor

Agonists (glucagon peptide): activate GCGR leading to increased blood glucose via hepatic glucose release. Antagonists: block GCGR to decrease hepatic glucose output, potentially useful in type 2 diabetes management.