Gastric inhibitory polypeptide (GIP), also known asglucose-dependent insulinotropic polypeptide, is aninhibiting hormone of thesecretin family ofhormones.[5] While it is a weak inhibitor ofgastric acid secretion, its main role, being anincretin, is to stimulateinsulin secretion.[6]
GIP, along withglucagon-like peptide-1 (GLP-1), belongs to a class of molecules referred to asincretins,[7] which stimulate insulin release on oral food intake.
GIP is derived from a 153-amino acid proprotein encoded by the GIP gene and circulates as a biologically active 42-amino acid peptide. It is synthesized by K cells, which are found in themucosa of theduodenum and thejejunum of thegastrointestinal tract.[8]
Like allendocrinehormones, it is transported by blood.
Gastric inhibitory polypeptide receptors are seven-transmembrane proteins (GPCRs) found onbeta-cells in thepancreas.
It has traditionally been namedgastrointestinal inhibitory peptide orgastric inhibitory peptide and was found to decrease the secretion ofstomach acid[9] to protect thesmall intestine from acid damage, reduce the rate at whichfood is transferred through thestomach, and inhibit the GI motility and secretion of acid. However, this is incorrect, as it was discovered that these effects are achieved only with higher-than-normal physiological level, and that these results naturally occur in the body through a similarhormone,secretin.[10]
It is now believed that the function of GIP is to induceinsulin secretion, which is stimulated primarily byhyperosmolarity ofglucose in the duodenum.[11] After this discovery, some researchers prefer the new name ofglucose-dependent insulinotropic peptide, while retaining theacronym "GIP." The amount of insulin secreted is greater when glucose is administered orally than intravenously.[12]
In addition to its role as an incretin, GIP is known to inhibitapoptosis of the pancreatic beta cells and to promote their proliferation. It also stimulatesglucagon secretion and fat accumulation. GIP receptors are expressed in many organs and tissues including thecentral nervous system enabling GIP to influencehippocampal memory formation and regulation of appetite and satiety.[13]
GIP recently appeared as a major player inbone remodeling. Researchers at Universities of Angers and Ulster evidenced that genetic ablation of the GIP receptor in mice resulted in profound alterations of bone microarchitecture through modification of the adipokine network.[14] Furthermore, the deficiency in GIP receptors has also been associated in mice with a dramatic decrease in bone quality and a subsequent increase in fracture risk.[15] However, the results obtained by these groups are far from conclusive because their animal models give discordant answers and these works should be analysed very carefully.[citation needed]
It has been found thattype 2 diabetics are not responsive to GIP and have lower levels of GIP secretion after a meal when compared to non-diabetics.[16] In research involvingknockout mice, it was found that absence of the GIP receptors correlates with resistance toobesity.[17]
Tirzepatide is ananalog of the human GIP hormone with a C20fatty diacid portion attached, that has been approved for treatment ofdiabetes in the US in May 2022.
