Glucagon-like peptide 1 receptor and Gastric inhibitory polypeptide receptor (GLP-1R and GIPR)

The Glucagon-like peptide 1 receptor (GLP-1R) and Gastric inhibitory polypeptide receptor (GIPR) are class B G protein-coupled receptors. GLP-1R is expressed in pancreatic β-cells, certain neurons, and other tissues, mediating the incretin effect of GLP-1 to enhance insulin secretion, suppress glucagon release, delay gastric emptying, reduce appetite, and support β-cell survival. GIPR is similarly distributed and mediates the actions of GIP, promoting insulin secretion in response to oral glucose. Both receptors feature seven transmembrane domains, an extracellular ligand-binding domain, and intracellular loops that interact with G proteins to trigger cAMP-dependent signaling. They are central to the pharmacological management of type 2 diabetes and obesity. Recently, drugs targeting both receptors (dual or triple agonists) have demonstrated superior metabolic efficacy by harnessing the complementary biology of GLP-1R and GIPR.

Other names

GLP1Rglucagon-like peptide-1 receptorGIP receptorglucose-dependent insulinotropic polypeptide receptorGIP receptor protein

Agonists mimic endogenous incretin hormones (GLP-1, GIP); they increase insulin secretion (glucose-dependent), decrease glucagon secretion, slow gastric emptying (GLP-1R), reduce appetite (GLP-1R), and enhance β-cell survival and proliferation (mainly GLP-1R).