Amylin receptor 2 (AMY2) (AMY2)

The Amylin receptor 2 (AMY2) is a heterodimeric G protein-coupled receptor (GPCR) complex formed by the association of the calcitonin receptor (CTR) and the receptor activity-modifying protein 2 (RAMP2) [1, 2]. It functions as a high-affinity receptor for the peptide hormone amylin, which is co-secreted with insulin by pancreatic beta cells to assist in postprandial glucose regulation [3]. Upon binding its ligand, AMY2 activates Gs-protein signaling pathways, leading to an increase in intracellular cyclic AMP (cAMP) levels [2, 4]. Biologically, the receptor is expressed in key brain regions like the area postrema, where it mediates satiety signals to reduce food intake and body weight [5]. Additionally, AMY2 activation slows gastric emptying and suppresses the secretion of glucagon, effectively lowering postprandial blood glucose excursions [3, 6]. Because of these metabolic effects, AMY2 is a primary therapeutic target for treating type 2 diabetes and obesity [6]. Drugs such as the synthetic amylin analog pramlintide and the long-acting agonist cagrilintide utilize this receptor to improve glycemic control and induce weight loss in clinical settings [7, 8].

Other names

CTR/RAMP2 complexCALCR/RAMP2Amylin receptor subtype 2

Agonism of the AMY2 receptor complex, which is a heterodimer of the calcitonin receptor and RAMP2, leads to the activation of Gs-mediated signaling, increasing intracellular cAMP levels to regulate satiety and glucose metabolism [2, 4].