Duodenum, Gastrin, Hormones, Peptides
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Gastric inhibitory peptide aka GIP and receptors

Gastric inhibitory polypeptide or gastric inhibitory peptide also known as glucose-dependent insulinotropic polypeptide abbreviated as GIP, is an inhibiting hormone of the secretin family of hormones.

While it is a weak inhibitor of gastric acid secretion, its main role is to stimulate insulin secretion.

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

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.

  • Costanzo, Linda (2014). Physiology. Philadelphia, PA: Saunders/Elsevier. p. 337. ISBN 9781455708475.

Like all endocrine hormones, it is transported by blood.[citation needed]

GIP-R is a member of the 7-transmembrane protein family, a class of G protein coupled receptors.

GIP-R is found on beta-cells in the pancreas where it serves as the receptor for the hormone Gastric inhibitory polypeptide (GIP)..

The gastric inhibitory polypeptide receptor (GIP-R), also known as the glucose-dependent insulinotropic polypeptide receptor, is a protein that in humans is encoded by the GIPR gene.

Functions

Gastric inhibitory polypeptide, also called glucose-dependent insulinotropic polypeptide, is a 42-amino acid polypeptide synthesized by K cells of the duodenum and small intestine. It was originally identified as an activity in gut extracts that inhibited gastric acid secretion and gastrin release, but subsequently was demonstrated to stimulate insulin release potently in the presence of elevated glucose. The insulinotropic effect on pancreatic islet beta-cells was then recognized to be the principal physiologic action of GIP. Together with glucagon-like peptide-1, GIP is largely responsible for the secretion of insulin after eating. It is involved in several other facets of the anabolic response.

It has traditionally been named gastrointestinal inhibitory peptide or gastric inhibitory peptide and was found to decrease the secretion of stomach acid 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 GIP is to induce insulin secretion, which is stimulated primarily by hyperosmolarity of glucose in the duodenum.

  • Thorens B (Dec 1995). “Glucagon-like peptide-1 and control of insulin secretion”. Diabète & Métabolisme. 21 (5): 311–8. PMID 8586147.

After this discovery, some researchers prefer the new name of glucose-dependent insulinotropic peptide, while retaining the acronym “GIP.” The amount of insulin secreted is greater when glucose is administered orally than intravenously.

  • Boron WF, Boulpaep EL (2009). Medical physiology: a cellular and molecular approach (2nd International ed.). Philadelphia, PA: Saunders/Elsevier. ISBN 9781416031154.

In addition to its role as an incretin, GIP is known to inhibit apoptosis of the 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 the central nervous system enabling GIP to influence hippocampal memory formation and regulation of appetite and satiety.

GIP recently appeared as a major player in bone 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.

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.

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]

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.

  • 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. doi:10.33549/physiolres.931893. PMID 20406045.

In research involving knockout mice, it was found that absence of the GIP receptors correlates with resistance to obesity.

  • 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. PMID 15655707.

References

  1. GRCh38: Ensembl release 89: ENSG00000159224 – Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000014351 – Ensembl, May 2017
  3. “Human PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. “Mouse PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Meier JJ, Nauck MA (2005). “Glucagon-like peptide 1(GLP-1) in biology and pathology”. Diabetes/Metabolism Research and Reviews. 21 (2): 91–117. doi:10.1002/dmrr.538. PMID 15759282. S2CID 39547553.
  6. Pederson RA, McIntosh CH (2016). “Discovery of gastric inhibitory polypeptide and its subsequent fate: Personal reflections”. Journal of Diabetes Investigation. 7 Suppl 1: 4–7. doi:10.1111/jdi.12480. PMC 4854497. PMID 27186348.
  7. Efendic S, Portwood N (2004). “Overview of incretin hormones”. Hormone and Metabolic Research. 36 (11–12): 742–6. doi:10.1055/s-2004-826157. PMID 15655702.
  8. Costanzo, Linda (2014). Physiology. Philadelphia, PA: Saunders/Elsevier. p. 337. ISBN 9781455708475.
  9. Kim W, Egan JM (Dec 2008). “The role of incretins in glucose homeostasis and diabetes treatment”. Pharmacological Reviews. 60 (4): 470–512. doi:10.1124/pr.108.000604. PMC 2696340. PMID 19074620.
  10. Creutzfeldt, Werner; Ebert, Reinhold; Ørskov, Cathrine; Bartels, Eckart; Nauck, Michael A. (1992). “Lack of Effect of Synthetic Human Gastric Inhibitory Polypeptide and Glucagon-LikePeptide 1 [7-36 Amide] Infused at Near-Physiological Concentrations on Pentagastrin-Stimulated Gastric Acid Secretion in Normal Human Subjects”. Digestion. 52 (3–4): 214–221. doi:10.1159/000200956. ISSN 0012-2823. PMID 1459356.
  11. Thorens B (Dec 1995). “Glucagon-like peptide-1 and control of insulin secretion”. Diabète & Métabolisme. 21 (5): 311–8. PMID 8586147.
  12. Boron WF, Boulpaep EL (2009). Medical physiology: a cellular and molecular approach (2nd International ed.). Philadelphia, PA: Saunders/Elsevier. ISBN 9781416031154.
  13. Seino, Yutaka; Fukushima, Mitsuo; Yabe, Daisuke (2010). “GIP and GLP-1, the two incretin hormones: Similarities and differences”. Journal of Diabetes Investigation. 1 (1–2): 8–23. doi:10.1111/j.2040-1124.2010.00022.x. PMC 4020673. PMID 24843404.
  14. Gaudin-Audrain C, Irwin N, Mansur S, Flatt PR, Thorens B, Baslé M, Chappard D, Mabilleau G (Mar 2013). “Glucose-dependent insulinotropic polypeptide receptor deficiency leads to modifications of trabecular bone volume and quality in mice” (PDF). Bone. 53 (1): 221–30. doi:10.1016/j.bone.2012.11.039. PMID 23220186. S2CID 36280105. Archived from the original (PDF) on 2018-07-21. Retrieved 2018-11-20.
  15. 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” (PDF). Bone. 56 (2): 337–42. doi:10.1016/j.bone.2013.07.003. PMID 23851294.
  16. 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. doi:10.33549/physiolres.931893. PMID 20406045.
  17. 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. PMID 15655707.
  18.  GRCh38: Ensembl release 89: ENSG00000010310 – Ensembl, May 2017
  19. GRCm38: Ensembl release 89: ENSMUSG00000030406 – Ensembl, May 2017
  20. “Human PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.
  21. “Mouse PubMed Reference:”. National Center for Biotechnology Information, U.S. National Library of Medicine.
  22. “Entrez Gene: gastric inhibitory polypeptide receptor”.
  23. Stoffel M, Fernald AA, Le Beau MM, Bell GI (August 1995). “Assignment of the gastric inhibitory polypeptide receptor gene (GIPR) to chromosome bands 19q13.2-q13.3 by fluorescence in situ hybridization”. Genomics. 28 (3): 607–609. doi:10.1006/geno.1995.1203. PMID 7490109.
  24. NCBI, NCBI Gene entry 2696 (GIPR), retrieved 2018-12-20.
  25. “Gastrointestinal Hormones and Peptides”. Retrieved 2007-08-24.
  26. Brubaker PL, Drucker DJ (2002). “Structure-function of the glucagon receptor family of G protein-coupled receptors: the glucagon, GIP, GLP-1, and GLP-2 receptors”. Recept. Channels. 8 (3–4): 179–188. doi:10.1080/10606820213687. PMID 12529935.

Further reading

External links

Hormones
Physiology of the gastrointestinal system
Peptides: neuropeptides

Categories: 

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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