glucose-dependent insulinotropic polypeptide[1-42]

Glucose-dependent insulinotropic polypeptide[1-42] (GIP[1-42]) is a 42-amino acid peptide hormone, also known as gastric inhibitory polypeptide. It is synthesized and secreted by K cells in the mucosa of the duodenum and jejunum of the small intestine in response to nutrient ingestion, especially fats and carbohydrates. As an incretin hormone, its primary physiological role is to stimulate glucose-dependent insulin secretion from pancreatic β-cells after food intake. This effect is mediated through binding to the GIP receptor (a GPCR) on β-cells, activating adenylyl cyclase via a stimulatory G protein (Gs), increasing intracellular cAMP levels, which then activate protein kinase A (PKA) and Epac2/cAMP-GEFII pathways. These cascades enhance calcium influx and promote exocytosis of insulin granules. Beyond its incretin effect, GIP has antiapoptotic properties that support pancreatic β-cell survival by activating signaling pathways such as Akt/PKB and CREB-mediated transcriptional regulation of antiapoptotic genes like bcl2 while downregulating proapoptotic genes like bax. Additional actions include promoting adipogenesis in adipose tissue, stimulating glucagon secretion under certain conditions, influencing bone remodeling via effects on osteoblasts/osteoclasts, modulating appetite/satiety through central nervous system receptors, and potentially affecting memory formation. GIP(1–42) is rapidly degraded in circulation by dipeptidyl peptidase IV (DPP-IV) into inactive forms such as GIP(3–42). The active form—GIP(1–42)—is used primarily for research purposes; it has not been developed or approved as a pharmaceutical drug for clinical use but serves as a key tool for studying metabolic diseases including type 2 diabetes mellitus and obesity.[1][3][4][6]

Other names

gastric inhibitory polypeptide[1-42]GIP(1-42)incretin hormone GIP