Gastric inhibitory polypeptide
Gastric inhibitory polypeptide (GIP), also known as glucose-dependent insulinotropic polypeptide, is an inhibiting hormone of the secretin family of hormones.[5] While it is a weak inhibitor of gastric acid secretion, its main role, being an incretin, is to stimulate insulin secretion.[6]
GIP, along with glucagon-like peptide-1 (GLP-1), belongs to a class of molecules (incretins)[7] which stimulate insulin release on oral food intake.
Synthesis and transport
[edit]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.[8]
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
[edit]GIP initially derived its name from its inhibitory effect on stomach acid secretion,[9] 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.[10]
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.[11] 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.[12]
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.[13] As of 2013[update], 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.[14] 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.[15] However, the results of the two groups' studies were non-concordant.
Pathology
[edit]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.[16] In research involving knockout mice, it was found that absence of the GIP receptors correlates with resistance to obesity.[17]
Tirzepatide
[edit]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.
References
[edit]- 1 2 3 GRCh38: Ensembl release 89: ENSG00000159224 – Ensembl, May 2017
- 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000014351 – Ensembl, May 2017
- ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ↑ 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.
- ↑ Pederson RA, McIntosh CH (April 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.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ↑ Efendic S, Portwood N (2004). "Overview of incretin hormones". Hormone and Metabolic Research. 36 (11–12): 742–746. doi:10.1055/s-2004-826157. PMID 15655702. S2CID 11634548.
- ↑ Costanzo L (2014). Physiology. Philadelphia, PA: Saunders/Elsevier. p. 337. ISBN 9781455708475.
- ↑ Kim W, Egan JM (December 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.
- ↑ Nauck MA, Bartels E, Orskov C, Ebert R, Creutzfeldt W (1992). "Lack of effect of synthetic human gastric inhibitory polypeptide and glucagon-like peptide 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. PMID 1459356.
- ↑ Thorens B (December 1995). "Glucagon-like peptide-1 and control of insulin secretion". Diabète & Métabolisme. 21 (5): 311–318. PMID 8586147.
- ↑ Boron WF, Boulpaep EL (2009). Medical physiology: a cellular and molecular approach (2nd International ed.). Philadelphia, PA: Saunders/Elsevier. ISBN 9781416031154.
- ↑ Seino Y, Fukushima M, Yabe D (April 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.
- ↑ Gaudin-Audrain C, Irwin N, Mansur S, Flatt PR, Thorens B, Baslé M, et al. (March 2013). "Glucose-dependent insulinotropic polypeptide receptor deficiency leads to modifications of trabecular bone volume and quality in mice" (PDF). Bone. 53 (1): 221–230. 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.
- ↑ Mieczkowska A, Irwin N, Flatt PR, Chappard D, Mabilleau G (October 2013). "Glucose-dependent insulinotropic polypeptide (GIP) receptor deletion leads to reduced bone strength and quality" (PDF). Bone. 56 (2): 337–342. doi:10.1016/j.bone.2013.07.003. PMID 23851294. S2CID 19296511.
- ↑ 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): 749–755. doi:10.33549/physiolres.931893. PMID 20406045.
- ↑ Yamada Y, Seino Y (2004). "Physiology of GIP--a lesson from GIP receptor knockout mice". Hormone and Metabolic Research. 36 (11–12): 771–774. doi:10.1055/s-2004-826162. PMID 15655707. S2CID 262453421.
External links
[edit]- Gastric+inhibitory+polypeptide at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- King MW (16 November 2006). "Gastrointestinal Hormones and Peptides". Indiana University – Purdue University Indianapolis School of Medicine. Archived from the original on 6 December 2007. Retrieved 1 October 2006.
- Overview of all the structural information available in the PDB for UniProt: P09681 (Gastric inhibitory polypeptide) at the PDBe-KB.