Gastric inhibitory polypeptide receptor (GIPR)

The gastric inhibitory polypeptide receptor (Gastric inhibitory polypeptide receptor, abbreviated as GIPR) is a class B1 G protein-coupled receptor that serves as the primary binding site for the hormone gastric inhibitory polypeptide—also known as glucose-dependent insulinotropic polypeptide. It is encoded by the *GIPR* gene. The main physiological function of this receptor is to mediate the incretin effect by stimulating insulin release from pancreatic β-cells following food intake, thereby playing a crucial role in postprandial glucose homeostasis. Beyond its actions on pancreatic cells, it also influences lipid metabolism by promoting fatty acid uptake into peripheral tissues such as adipocytes, modulates bone remodeling through effects on osteoblasts/osteoclasts, and has emerging roles within neurosignaling pathways due to its expression in brain regions. Therapeutically, targeting this pathway has become increasingly important with the advent of dual GLP‑1/GIP agonists like tirzepatide for type 2 diabetes mellitus and obesity management. However, challenges remain regarding its potential obesogenic properties when overstimulated and reduced responsiveness (“resistance”) observed in diabetic patients. Research continues into selective modulation strategies that could maximize metabolic benefits while minimizing adverse outcomes related to weight gain or inflammation.[1][2][3][4][5]

Other names

Glucose-dependent insulinotropic polypeptide receptorGIP receptorGIP-R

Agonists mimic endogenous GIP to stimulate the receptor, enhancing glucose-dependent insulin secretion from pancreatic β-cells. Dual agonists (e.g., tirzepatide) activate both GLP‑1 and GIP receptors for synergistic effects on glycemic control and weight loss. Antagonism or modulation may affect adiposity or inflammatory pathways.