Gastric inhibitory polypeptide (GIP), also known as glucose-dependent insulinotropic polypeptide, is an inhibiting hormone of the secretin family of hormones. While it is a weak inhibitor of gastric acid secretion, its main role, being an incretin, is to stimulate insulin secretion.
GIP, along with glucagon-like peptide-1 (GLP-1), belongs to a class of molecules (incretins) which stimulate insulin release on oral food intake.
Synthesis and transport 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 the mucosa of the duodenum and the jejunum of the gastrointestinal tract.
Like all endocrine hormones, it is transported by the blood. Gastric inhibitory polypeptide receptors are seven-transmembrane protein (GPCRs) found in beta cells in the pancreas.
Functions GIP initially derived its name from its inhibitory effect on stomach acid secretion, its ability to protect the small intestine from acid-induced damage, its slowing of the pace with which consumed foods exit the stomach, and its reduction of general gastrointestinal motility. However, the initially hypothesized mechanism was incorrect, as it was later discovered that the hormone achieved its effects only when its concentration exceeded basal physiologic levels and that it operated similarly to secretin.
It is now believed that GIP primarily acts as an inducer of insulin secretion, which is stimulated primarily by hyperosmolarity of glucose in the duodenum. Since its mechanism was uncovered in 1995, the hormone has sometimes been referred to as glucose-dependent insulinotropic peptide, while retaining the acronym GIP. The amount of insulin secreted is greater when glucose is administered orally than intravenously.
In addition to its role as an incretin, GIP is known to inhibit apoptosis of pancreatic beta cells and to promote their proliferation. It also stimulates glucagon secretion and fat accumulation. GIP receptors are expressed in many organs and tissues including those of the central nervous system, enabling regulation of appetite and satiety. , GIP was believed to be an important driver of bone remodeling. Researchers at the Universities of Angers and Ulster noted that genetic ablation of the GIP receptor in mice resulted in profound alterations of bone microarchitecture through modification of the adipokine network. Furthermore, a deficiency in GIP receptors has been associated in mice with a dramatic decrease in bone quality and a subsequent increase in fracture risk. However, the results of the two groups' studies were non-concordant.
Pathology It has been found that type 2 diabetics are not responsive to GIP and have lower levels of GIP secretion after a meal when compared to non-diabetics. In research involving knockout mice, it was found that absence of the GIP receptors correlates with resistance to obesity.
Tirzepatide Tirzepatide is an analog of the human GIP hormone with a C20 fatty diacid portion attached, which has been approved for treatment of diabetes in the U.S. in May 2022.
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