Amylin receptor type 1 (AMY1) (AMY1)

The Amylin receptor type 1 (AMY1) is a heterodimeric G protein-coupled receptor (GPCR) complex formed by the association of the calcitonin receptor (CTR) and the receptor activity-modifying protein 1 (RAMP1) [PMID: 25231138]. It belongs to the Class B GPCR family and is primarily activated by amylin, a 37-amino acid peptide hormone co-secreted with insulin by pancreatic beta cells in response to nutrient intake [PMID: 29124050]. AMY1 is highly expressed in the area postrema of the brainstem, where it plays a pivotal role in metabolic regulation by inducing satiety, slowing gastric emptying, and suppressing postprandial glucagon secretion [PMID: 22414320]. These physiological actions make AMY1 a high-value therapeutic target for metabolic disorders. The synthetic amylin analog pramlintide is currently the only FDA-approved drug targeting this receptor for the treatment of type 1 and type 2 diabetes [StatPearls: NBK539734]. Furthermore, the development of long-acting amylin receptor agonists, such as cagrilintide, has shown significant promise in clinical trials for the treatment of obesity, either as monotherapy or in combination with GLP-1 receptor agonists [PMID: 33915093]. Therapeutic challenges associated with AMY1 agonists primarily include dose-dependent gastrointestinal side effects like nausea and the risk of hypoglycemia when used alongside insulin therapy.

Other names

CTR/RAMP1 complexCalcitonin receptor:RAMP1 complexAmylin 1 receptorAMY1 receptor

Agonism of the AMY1 receptor complex activates the Gs protein-adenylyl cyclase pathway, leading to increased intracellular cAMP and subsequent signaling that modulates appetite and glucose metabolism.