Mouse gastric inhibitory polypeptide receptor (GIPR) (GIPR)

The Mouse gastric inhibitory polypeptide receptor (GIPR) is a Class B G protein-coupled receptor that plays a central role in the incretin effect, mediating glucose-dependent insulin secretion from pancreatic beta cells (UniProt Q0P544). The extracellular domain (ECD) of the mouse GIPR is a critical structural component that facilitates the initial high-affinity binding of the GIP peptide, which is necessary for subsequent receptor activation and signaling (PubMed: 17493937). Beyond the pancreas, GIPR is expressed in adipose tissue and the central nervous system, where it regulates lipid metabolism and energy homeostasis (NCBI Gene: 14607). In drug development, GIPR is a major therapeutic target for metabolic disorders; for example, the dual GLP-1 and GIP receptor agonist Tirzepatide has demonstrated significant efficacy in reducing body weight and improving glycemic control in both mouse models and human clinical trials (PubMed: 34437088). Interestingly, research using GIPR-deficient mice has shown that the absence of GIPR signaling can protect against diet-induced obesity, suggesting that both agonism and antagonism of this pathway may have therapeutic potential (PubMed: 11742398). The mouse GIPR ECD is frequently utilized in structural biology and screening assays to identify novel ligands and multi-receptor agonists like Retatrutide (PubMed: 37366315).

Other names

Glucose-dependent insulinotropic polypeptide receptorGIP receptorGiprIncretin receptor

Agonism of the receptor stimulates glucose-dependent insulin secretion from pancreatic beta cells and modulates lipid metabolism in adipose tissue; it is often targeted in combination with GLP-1 receptors to synergistically improve metabolic health (PubMed: 34437088).