Glucose-dependent insulinotropic polypeptide receptor (GIPR) (GIPR)

The Glucose-dependent insulinotropic polypeptide receptor (GIPR) is a member of the Class B G protein-coupled receptor (GPCR) family and is a key mediator of the incretin effect (UniProt P43219). It is primarily expressed in pancreatic beta cells, where it stimulates insulin secretion in response to the hormone GIP, which is released from the gut after nutrient ingestion (PubMed: 16413408). The extracellular domain (ECD) of the receptor, particularly in mouse models, is a critical structural component that facilitates high-affinity binding of the GIP peptide and is often used in drug screening and structural biology studies (PubMed: 30531903). Beyond its insulinotropic effects, GIPR signaling influences lipid metabolism in adipose tissue and energy homeostasis in the central nervous system. In the context of disease, GIPR is a major therapeutic target for type 2 diabetes and obesity, as its activation helps regulate blood glucose and reduce body weight. Modern therapies like tirzepatide act as dual agonists for both GIPR and the GLP-1 receptor to achieve superior metabolic outcomes compared to mono-agonists (PubMed: 35567573). Safety profiles for GIPR-targeted drugs generally involve manageable gastrointestinal side effects, though long-term monitoring for pancreatic and gallbladder health is standard in clinical practice.

Other names

Gastric inhibitory polypeptide receptorGIP receptorGipr

Agonism of the GIP receptor activates adenylyl cyclase, leading to increased intracellular cAMP levels which enhances glucose-dependent insulin secretion from pancreatic beta cells.