Amylin receptor (AMYR) (AMYR)

Amylin receptors are complex heterodimeric G protein-coupled receptors (GPCRs) formed by the association of the calcitonin receptor (CTR) with one of three receptor activity-modifying proteins (RAMP1, RAMP2, or RAMP3) [2, 4, 12]. These combinations result in three distinct subtypes: AMY1, AMY2, and AMY3, which exhibit varying affinities for amylin and related peptides like calcitonin gene-related peptide (CGRP) [6, 16, 17]. Amylin, a 37-amino acid peptide hormone co-secreted with insulin from pancreatic beta cells, is the primary endogenous ligand [1, 11, 20]. Activation of these receptors, particularly in the brainstem's area postrema, plays a vital role in metabolic regulation by promoting satiety, slowing gastric emptying, and suppressing postprandial glucagon secretion [3, 7, 10]. In metabolic diseases such as type 2 diabetes and obesity, amylin signaling is often impaired, and the endogenous peptide can form toxic amyloid aggregates that contribute to pancreatic beta-cell dysfunction [10, 14, 20]. Therapeutic interventions primarily utilize amylin receptor agonists to restore these regulatory functions, with pramlintide being the first FDA-approved analog for diabetes [1, 8, 15]. Modern drug development is focused on long-acting dual agonists (DACRAs) and unimolecular co-agonists to achieve superior weight loss and glycemic control [4, 18, 19]. Beyond metabolism, amylin receptors are investigated for their roles in migraine pathophysiology due to CGRP cross-reactivity and in Alzheimer's disease, where they may influence amyloid-beta clearance and neurotoxicity [6, 10, 14].

Other names

Islet amyloid polypeptide receptorIAPP receptorAMY1 receptorAMY2 receptorAMY3 receptorCalcitonin receptor/RAMP complex

Amylin receptor agonist, Dual amylin and calcitonin receptor agonist (DACRA), Dual amylin and GLP-1 receptor agonist, Amylin receptor antagonist