Gastric inhibitory peptide

Gastric inhibitory peptide (GIP) also known as gastric inhibitory polypeptide or glucose-dependent insulinotropic peptide, is an inhibiting hormone of the secretin family of hormones ¹. While gastric inhibitory polypeptide is weak inhibitor of gastric acid secretion, its main role is to stimulate insulin secretion ². Like all endocrine hormones, it is transported by blood. Gastric inhibitory polypeptide receptors are seven-transmembrane proteins found on beta-cells in the pancreas.

Gastric inhibitory peptide along with glucagon-like peptide-1 (GLP-1), belongs to a class of molecules referred to as incretins ³.

Gastric inhibitory polypeptide 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 ⁴.

Gastric inhibitory peptide function

Gastric inhibitory polypeptide has traditionally been named gastrointestinal inhibitory peptide or gastric inhibitory peptide and was found to decrease the secretion of stomach acid ⁵ to protect the small intestine from acid damage, reduce the rate at which food is transferred through the stomach, 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 similar hormone, secretin.

It is now believed that the function of gastric inhibitory peptide is to induce insulin secretion, which is stimulated primarily by hyperosmolarity of glucose in the duodenum ⁶. After this discovery, some researchers prefer the new name of glucose-dependent insulinotropic peptide, while retaining the acronym “GIP” ⁷. The amount of insulin secreted is greater when glucose is administered orally than intravenously ⁸.

In addition to gastric inhibitory polypeptide role as an incretin, gastric inhibitory peptide is known to inhibit apoptosis of the pancreatic beta cells and to promote their proliferation. It also stimulates glucagon secretion and fat accumulation. gastric inhibitory peptide receptors are expressed in many organs and tissues including the central nervous system enabling gastric inhibitory peptide to influence hippocampal memory formation and regulation of appetite and satiety ⁹.

Gastric inhibitory peptide recently appeared as a major player in bone remodeling. Researchers at Universities of Angers and Ulster evidenced that genetic ablation of the gastric inhibitory peptide receptor in mice resulted in profound alterations of bone microarchitecture through modification of the adipokine network ¹⁰. Furthermore, the deficiency in gastric inhibitory peptide receptors has also been associated in mice with a dramatic decrease in bone quality and a subsequent increase in fracture risk ¹¹. However, the results obtained by these groups are far from conclusive because their animal models give discordant answers and these works should be analyzed very carefully.

It has been found that type 2 diabetics are not responsive to gastric inhibitory peptide and have lower levels of gastric inhibitory peptide secretion after a meal when compared to non-diabetics ¹². In research involving knockout mice, it was found that absence of the gastric inhibitory peptide receptors correlates with resistance to obesity ¹³.

References

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2. Pederson RA, McIntosh CH. Discovery of gastric inhibitory polypeptide and its subsequent fate: Personal reflections. J Diabetes Investig. 2016;7 Suppl 1(Suppl 1):4–7. doi:10.1111/jdi.12480 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4854497
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6. Thorens B (Dec 1995). “Glucagon-like peptide-1 and control of insulin secretion”. Diabète & Métabolisme. 21 (5): 311–8. https://www.ncbi.nlm.nih.gov/pubmed/8586147
7. Schauder P, Brown JC, Frerichs H, Creutzfeldt W: Gastric inhibitory polypeptide: effect on glucose-induced insulin release from isolated rat pancreatic islets in vitro. Diabetologia11 :483 –484,1975
8. Boron WF, Boulpaep EL (2009). Medical physiology: a cellular and molecular approach (2nd International ed.). Philadelphia, PA: Saunders/Elsevier. ISBN 9781416031154.
9. Seino Y, Fukushima M, Yabe D. GIP and GLP-1, the two incretin hormones: Similarities and differences. J Diabetes Investig. 2010;1(1-2):8–23. doi:10.1111/j.2040-1124.2010.00022.x https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4020673
10. Glucose-dependent insulinotropic polypeptide receptor deficiency leads to modifications of trabecular bone volume and quality in mice. Bone. 2013 Mar;53(1):221-30. doi: 10.1016/j.bone.2012.11.039. Epub 2012 Dec 6. https://doi.org/10.1016/j.bone.2012.11.039
11. Mieczkowska A, Irwin N, Flatt PR, Chappard D, Mabilleau G (Oct 2013). “Glucose-dependent insulinotropic polypeptide (GIP) receptor deletion leads to reduced bone strength and quality”. Bone. 56 (2): 337–42. doi:10.1016/j.bone.2013.07.003 https://doi.org/10.1016/j.bone.2013.07.003
12. Skrha J, Hilgertová J, Jarolímková M, Kunešová M, Hill M (2010). “Meal test for glucose-dependent insulinotropic peptide (GIP) in obese and type 2 diabetic patients”. Physiological Research. 59 (5): 749–55 http://www.biomed.cas.cz/physiolres/pdf/59/59_749.pdf
13. Yamada Y, Seino Y (2004). “Physiology of GIP–a lesson from GIP receptor knockout mice”. Hormone and Metabolic Research. 36 (11–12): 771–4. doi:10.1055/s-2004-826162