Gastric inhibitory polypeptide receptor (GIPR) (GIPR)

The Gastric inhibitory polypeptide receptor (GIPR), also known as the glucose-dependent insulinotropic polypeptide receptor, is a Class B G protein-coupled receptor primarily expressed in pancreatic beta cells, adipose tissue, and the central nervous system [4, 7, 14]. Its primary physiological role is to mediate the "incretin effect," where the hormone GIP stimulates insulin secretion from the pancreas in response to oral nutrient intake [2, 14]. Beyond glycemic control, GIPR signaling influences lipid metabolism in adipose tissue and regulates energy balance through receptors in the brain's satiety centers [5, 11, 15]. In the context of disease, GIPR is a major therapeutic target for type 2 diabetes and obesity, where its modulation helps restore insulin sensitivity and promote weight loss [1, 6, 13]. Interestingly, both GIPR agonism (e.g., tirzepatide) and antagonism (e.g., maridebart cafraglutide) are being explored as therapeutic strategies, often in combination with GLP-1 receptor modulation [13, 17, 19]. While agonists enhance the insulinotropic response and central satiety, antagonists are thought to prevent GIP-mediated fat accumulation and potentially alleviate side effects like nausea [13, 19].

Other names

Glucose-dependent insulinotropic polypeptide receptor [4, 16]GIP-R [16]PGQTL2 [16]

Agonism of the GIPR stimulates adenylate cyclase, increasing intracellular cAMP and potentiating glucose-dependent insulin secretion [14, 18]. Pharmacological agonism or antagonism (often in combination with GLP-1R) also modulates central energy balance and peripheral lipid storage to treat metabolic disorders [6, 13, 19].