Unacylated ghrelin receptor (UAGR)

The unacylated ghrelin receptor (UAGR) is the primary mediator for the biological actions of unacylated ghrelin (UAG), the most abundant form of ghrelin in human circulation (Broglio et al., 2004, J Clin Endocrinol Metab). Unlike acylated ghrelin, UAG does not bind to the growth hormone secretagogue receptor (GHSR-1a), leading to the initial belief that it was an inactive degradation product (Delhanty et al., 2012, Mol Cell Endocrinol). However, subsequent research has identified specific high-affinity binding sites for UAG in various tissues, including the heart, skeletal muscle, and liver, though the exact molecular structure of the receptor is still being characterized, with some evidence pointing toward the scavenger receptor CD36 (Granata et al., 2010, J Biol Chem). The UAGR is involved in critical metabolic processes, such as the suppression of hepatic glucose output and the protection of pancreatic beta cells from apoptosis (Granata et al., 2007, Endocrinology). In skeletal muscle, UAGR signaling promotes myoblast differentiation and protects against atrophy, making it a target for treating cachexia and sarcopenia (Filigheddu et al., 2007, FASEB J). Clinically, the UAGR is a target for metabolic diseases because UAG acts as a functional antagonist to the metabolic effects of acylated ghrelin, improving insulin sensitivity (Allas et al., 2016, PLOS ONE). Drug development efforts have focused on UAG analogs, such as lunitide (AZP-531), which are designed to treat conditions like Prader-Willi syndrome and Type 2 diabetes by leveraging these insulin-sensitizing and anorexigenic properties (Amryt Pharma, 2021).

Other names

Des-acyl ghrelin receptorDes-octanoyl ghrelin receptorUAG receptorPutative unacylated ghrelin receptor

Agonism of the unacylated ghrelin receptor to improve insulin sensitivity and counteract acylated ghrelin-mediated metabolic dysfunction.