Biology:Glucose-dependent insulinotropic polypeptide

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Short description: Mammalian protein found in Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Glucose-dependent insulinotropic polypeptide (more commonly known earlier as gastric inhibitory polypeptide or gastric inhibitory peptide), abbreviated as GIP, is an inhibiting hormone of the secretin family of hormones.[1] While it is a weak inhibitor of gastric acid secretion, its main role, being an incretin, is to stimulate insulin secretion.[2]

GIP, along with glucagon-like peptide-1 (GLP-1), belongs to a class of molecules referred to as incretins,[3] 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.[4]

Like all endocrine hormones, it is transported by blood.

Gastric inhibitory polypeptide receptors are seven-transmembrane proteins (GPCRs) found on beta-cells in the pancreas.

Functions

It 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.[6]

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.[7] 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.[8]

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.[9]

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.[10] 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.[11] 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.[12] In research involving knockout mice, it was found that absence of the GIP receptors correlates with resistance to obesity.[13]

References

  1. ↑ "Glucagon-like peptide 1(GLP-1) in biology and pathology". Diabetes/Metabolism Research and Reviews 21 (2): 91–117. 2005. doi:10.1002/dmrr.538. PMID 15759282. 
  2. ↑ "Discovery of gastric inhibitory polypeptide and its subsequent fate: Personal reflections". Journal of Diabetes Investigation 7 (Suppl 1): 4–7. 2016. doi:10.1111/jdi.12480. PMID 27186348. 
  3. ↑ "Overview of incretin hormones". Hormone and Metabolic Research 36 (11–12): 742–6. 2004. doi:10.1055/s-2004-826157. PMID 15655702. 
  4. ↑ Costanzo, Linda (2014). Physiology. Philadelphia, PA: Saunders/Elsevier. pp. 337. ISBN 9781455708475. 
  5. ↑ "The role of incretins in glucose homeostasis and diabetes treatment". Pharmacological Reviews 60 (4): 470–512. Dec 2008. doi:10.1124/pr.108.000604. PMID 19074620. 
  6. ↑ 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"] (in en). Digestion 52 (3–4): 214–221. doi:10.1159/000200956. ISSN 0012-2823. PMID 1459356. https://www.karger.com/Article/FullText/200956. 
  7. ↑ "Glucagon-like peptide-1 and control of insulin secretion". Diabète & Métabolisme 21 (5): 311–8. Dec 1995. PMID 8586147. 
  8. ↑ Boron, Walter F.; Boulpaep, Emile L. (2009). Medical physiology: a cellular and molecular approach (2nd International ed.). Philadelphia, PA: Saunders/Elsevier. ISBN 9781416031154. 
  9. ↑ 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. PMID 24843404. 
  10. ↑ "Glucose-dependent insulinotropic polypeptide receptor deficiency leads to modifications of trabecular bone volume and quality in mice". Bone 53 (1): 221–30. Mar 2013. doi:10.1016/j.bone.2012.11.039. PMID 23220186. http://eprints.uthm.edu.my/8086/1/Dr._Sity_Aishah.pdf. Retrieved 2018-11-20. 
  11. ↑ "Glucose-dependent insulinotropic polypeptide (GIP) receptor deletion leads to reduced bone strength and quality". Bone 56 (2): 337–42. Oct 2013. doi:10.1016/j.bone.2013.07.003. PMID 23851294. https://hal.univ-angers.fr/hal-03262094/file/2013b-bone.pdf. 
  12. ↑ "Meal test for glucose-dependent insulinotropic peptide (GIP) in obese and type 2 diabetic patients". Physiological Research 59 (5): 749–55. 2010. doi:10.33549/physiolres.931893. PMID 20406045. 
  13. ↑ "Physiology of GIP--a lesson from GIP receptor knockout mice". Hormone and Metabolic Research 36 (11–12): 771–4. 2004. doi:10.1055/s-2004-826162. PMID 15655707. 

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