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Gene Review

Gip  -  gastric inhibitory polypeptide

Mus musculus

Synonyms: GIP, Gastric inhibitory polypeptide, Glucose-dependent insulinotropic polypeptide, glucose-dependent insulinotropic polypeptide
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Disease relevance of Gip


Psychiatry related information on Gip


High impact information on Gip

  • Wild-type mice fed a high-fat diet exhibited both hypersecretion of GIP and extreme visceral and subcutaneous fat deposition with insulin resistance [1].
  • A tumor-derived K-cell line was induced to produce human insulin by providing the cells with the human insulin gene linked to the 5'-regulatory region of the gene encoding glucose-dependent insulinotropic polypeptide (GIP) [7].
  • Mice with a targeted mutation of the gastric inhibitory polypeptide (GIP) receptor gene (GIPR) were generated to determine the role of GIP as a mediator of signals from the gut to pancreatic beta cells [8].
  • Accordingly, early insulin secretion mediated by GIP determines glucose tolerance after oral glucose load in vivo, and because GIP plays an important role in the compensatory enhancement of insulin secretion produced by a high insulin demand, a defect in this entero-insular axis may contribute to the pathogenesis of diabetes [8].
  • The hormonal factor(s) implicated as transmitters of signals from the gut to pancreatic beta-cells is referred to as incretin, and gastric inhibitory polypeptide (GIP) is identified as one of the incretins [9].

Chemical compound and disease context of Gip


Biological context of Gip


Anatomical context of Gip


Associations of Gip with chemical compounds


Physical interactions of Gip

  • Electromobility shift assays using STC-1 nuclear extracts demonstrated the specific binding of PDX-1 protein to a specific regulatory region in the GIP promoter [21].
  • RESULTS: The results reveal that glycation of the N-terminus of GLP-1 or GIP stabilized both peptides against DPP-IV degradation [22].

Regulatory relationships of Gip

  • In vitro studies demonstrated that GIP analogues retained their ability to activate the GIP receptor through production of cAMP and to stimulate insulin secretion [23].

Other interactions of Gip

  • Glucose-dependent insulinotrophic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are important enteroendocrine hormones that are rapidly degraded by an ubiquitous enzyme dipeptidyl peptidase IV to yield truncated metabolites GIP(3-42) and GLP-1(9-36)amide [24].
  • The incretins glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are gut hormones that act via the enteroinsular axis to potentiate insulin secretion from the pancreas in a glucose-dependent manner [25].
  • DIRKO mice exhibit normal body weight and fail to exhibit an improved glycemic response after exogenous administration of GIP or the GLP-1R agonist exendin-4 [26].
  • In mice lacking K(ATP) channels (Kir6.2(-/-) mice), we found that pretreatment with GIP in vivo failed to blunt the rise in blood glucose levels after oral glucose load [27].
  • Somatostatin release was similarly increased by GIP (10-1000 nmol/l) at both glucose concentrations [28].

Analytical, diagnostic and therapeutic context of Gip

  • Foxo1 bound to FHRE-II in gel mobility shift assays, and Foxo1-FHRE-II interactions conferred GIP responsiveness to the bax promoter [15].
  • Perfusion experiments of Kir6.2(-/-) mice revealed severely impaired potentiation of insulin secretion by 1 nmol/l GIP and substantial potentiation by 1 nmol/l GLP-1 [27].
  • Serum GIP levels in GLP-1R -/- mice were significantly elevated versus those in +/+ control mice after an oral glucose tolerance test (369 +/- 40 vs. 236 +/- 28 pmol/l; P < or = 0.02) [29].
  • Using immunohistochemistry, we verified the expression of PDX-1 protein in the nucleus of GIP-expressing mouse K-cells and evaluated the expression of PDX-1, serotonin, and GIP in wild-type and PDX-1(-/-) mice at 18.5 d after conception [21].
  • Using chromatin immunoprecipitation analysis, we demonstrated binding of PDX-1 to this same region of the GIP promoter in intact cells [21].


  1. Inhibition of gastric inhibitory polypeptide signaling prevents obesity. Miyawaki, K., Yamada, Y., Ban, N., Ihara, Y., Tsukiyama, K., Zhou, H., Fujimoto, S., Oku, A., Tsuda, K., Toyokuni, S., Hiai, H., Mizunoya, W., Fushiki, T., Holst, J.J., Makino, M., Tashita, A., Kobara, Y., Tsubamoto, Y., Jinnouchi, T., Jomori, T., Seino, Y. Nat. Med. (2002) [Pubmed]
  2. Evaluation of the antidiabetic activity of DPP IV resistant N-terminally modified versus mid-chain acylated analogues of glucose-dependent insulinotropic polypeptide. Irwin, N., Clarke, G.C., Green, B.D., Greer, B., Harriott, P., Gault, V.A., O'Harte, F.P., Flatt, P.R. Biochem. Pharmacol. (2006) [Pubmed]
  3. Abnormalities of GIP in spontaneous syndromes of obesity and diabetes in mice. Flatt, P.R., Bailey, C.J., Kwasowski, P., Swanston-Flatt, S.K., Marks, V. Diabetes (1983) [Pubmed]
  4. Cell-specific expression of the glucose-dependent insulinotropic polypeptide gene in a mouse neuroendocrine tumor cell line. Boylan, M.O., Jepeal, L.I., Jarboe, L.A., Wolfe, M.M. J. Biol. Chem. (1997) [Pubmed]
  5. Overexpression of a dominant negative GIP receptor in transgenic mice results in disturbed postnatal pancreatic islet and beta-cell development. Herbach, N., Goeke, B., Schneider, M., Hermanns, W., Wolf, E., Wanke, R. Regul. Pept. (2005) [Pubmed]
  6. Effects of glucose-dependent insulinotropic peptide on behavior. Ding, K.H., Zhong, Q., Xie, D., Chen, H.X., Della-Fera, M.A., Bollag, R.J., Bollag, W.B., Gujral, R., Kang, B., Sridhar, S., Baile, C., Curl, W., Lsales, C.M. Peptides (2006) [Pubmed]
  7. Glucose-dependent insulin release from genetically engineered K cells. Cheung, A.T., Dayanandan, B., Lewis, J.T., Korbutt, G.S., Rajotte, R.V., Bryer-Ash, M., Boylan, M.O., Wolfe, M.M., Kieffer, T.J. Science (2000) [Pubmed]
  8. Glucose intolerance caused by a defect in the entero-insular axis: a study in gastric inhibitory polypeptide receptor knockout mice. Miyawaki, K., Yamada, Y., Yano, H., Niwa, H., Ban, N., Ihara, Y., Kubota, A., Fujimoto, S., Kajikawa, M., Kuroe, A., Tsuda, K., Hashimoto, H., Yamashita, T., Jomori, T., Tashiro, F., Miyazaki, J., Seino, Y. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  9. Pancreatic and extrapancreatic effects of gastric inhibitory polypeptide. Yamada, Y., Miyawaki, K., Tsukiyama, K., Harada, N., Yamada, C., Seino, Y. Diabetes (2006) [Pubmed]
  10. Studies with GIP/Ins cells indicate secretion by gut K cells is KATP channel independent. Wang, S.Y., Chi, M.M., Li, L., Moley, K.H., Wice, B.M. Am. J. Physiol. Endocrinol. Metab. (2003) [Pubmed]
  11. Enhanced cAMP generation and insulin-releasing potency of two novel Tyr1-modified enzyme-resistant forms of glucose-dependent insulinotropic polypeptide is associated with significant antihyperglycaemic activity in spontaneous obesity-diabetes. Gault, V.A., Flatt, P.R., Bailey, C.J., Harriott, P., Greer, B., Mooney, M.H., O'harte, F.P. Biochem. J. (2002) [Pubmed]
  12. Gastric inhibitory polypeptide and insulin responses to orally administered amino acids in genetically obese hyperglycemic (ob/ob) mice. Flatt, P.R., Kwasowski, P., Howland, R.J., Bailey, C.J. J. Nutr. (1991) [Pubmed]
  13. Gastric inhibitory polypeptide and the entero-insular axis in streptozotocin diabetic mice. Bailey, C.J., Flatt, P.R., Kwasowski, P., Adams, M. Diabète & métabolisme. (1986) [Pubmed]
  14. Targeted ablation of glucose-dependent insulinotropic polypeptide-producing cells in transgenic mice reduces obesity and insulin resistance induced by a high fat diet. Althage, M.C., Ford, E.L., Wang, S., Tso, P., Polonsky, K.S., Wice, B.M. J. Biol. Chem. (2008) [Pubmed]
  15. Glucose-dependent insulinotropic polypeptide (GIP) stimulation of pancreatic beta-cell survival is dependent upon phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB) signaling, inactivation of the forkhead transcription factor Foxo1, and down-regulation of bax expression. Kim, S.J., Winter, K., Nian, C., Tsuneoka, M., Koda, Y., McIntosh, C.H. J. Biol. Chem. (2005) [Pubmed]
  16. Gastric inhibitory polypeptide as an endogenous factor promoting new bone formation after food ingestion. Tsukiyama, K., Yamada, Y., Yamada, C., Harada, N., Kawasaki, Y., Ogura, M., Bessho, K., Li, M., Amizuka, N., Sato, M., Udagawa, N., Takahashi, N., Tanaka, K., Oiso, Y., Seino, Y. Mol. Endocrinol. (2006) [Pubmed]
  17. Chemical ablation of gastric inhibitory polypeptide receptor action by daily (Pro3)GIP administration improves glucose tolerance and ameliorates insulin resistance and abnormalities of islet structure in obesity-related diabetes. Gault, V.A., Irwin, N., Green, B.D., McCluskey, J.T., Greer, B., Bailey, C.J., Harriott, P., O'harte, F.P., Flatt, P.R. Diabetes (2005) [Pubmed]
  18. A stable analogue of glucose-dependent insulinotropic polypeptide, GIP(LysPAL16), enhances functional differentiation of mouse embryonic stem cells into cells expressing islet-specific genes and hormones. Marenah, L., McCluskey, J.T., Abdel-Wahab, Y.H., O'Harte, F.P., McClenaghan, N.H., Flatt, P.R. Biol. Chem. (2006) [Pubmed]
  19. Glucose-dependent insulinotropic polypeptide receptor knockout mice have altered bone turnover. Xie, D., Cheng, H., Hamrick, M., Zhong, Q., Ding, K.H., Correa, D., Williams, S., Mulloy, A., Bollag, W., Bollag, R.J., Runner, R.R., McPherson, J.C., Insogna, K., Isales, C.M. Bone (2005) [Pubmed]
  20. Chronic exposure to GLP-1R agonists promotes homologous GLP-1 receptor desensitization in vitro but does not attenuate GLP-1R-dependent glucose homeostasis in vivo. Baggio, L.L., Kim, J.G., Drucker, D.J. Diabetes (2004) [Pubmed]
  21. Cell-specific expression of glucose-dependent-insulinotropic polypeptide is regulated by the transcription factor PDX-1. Jepeal, L.I., Fujitani, Y., Boylan, M.O., Wilson, C.N., Wright, C.V., Wolfe, M.M. Endocrinology (2005) [Pubmed]
  22. A comparison of the cellular and biological properties of DPP-IV-resistant N-glucitol analogues of glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide. Green, B.D., Gault, V.A., O'Harte, F.P., Flatt, P.R. Diabetes, obesity & metabolism. (2005) [Pubmed]
  23. GIP(Lys16PAL) and GIP(Lys37PAL): novel long-acting acylated analogues of glucose-dependent insulinotropic polypeptide with improved antidiabetic potential. Irwin, N., O'Harte, F.P., Gault, V.A., Green, B.D., Greer, B., Harriott, P., Bailey, C.J., Flatt, P.R. J. Med. Chem. (2006) [Pubmed]
  24. Effects of sub-chronic exposure to naturally occurring N-terminally truncated metabolites of glucose-dependent insulinotrophic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), GIP(3-42) and GLP-1(9-36)amide, on insulin secretion and glucose homeostasis in ob/ob mice. Parker, J.C., Lavery, K.S., Irwin, N., Green, B.D., Greer, B., Harriott, P., O'harte, F.P., Gault, V.A., Flatt, P.R. J. Endocrinol. (2006) [Pubmed]
  25. Glucose-dependent insulinotropic polypeptide receptor null mice exhibit compensatory changes in the enteroinsular axis. Pamir, N., Lynn, F.C., Buchan, A.M., Ehses, J., Hinke, S.A., Pospisilik, J.A., Miyawaki, K., Yamada, Y., Seino, Y., McIntosh, C.H., Pederson, R.A. Am. J. Physiol. Endocrinol. Metab. (2003) [Pubmed]
  26. Double incretin receptor knockout (DIRKO) mice reveal an essential role for the enteroinsular axis in transducing the glucoregulatory actions of DPP-IV inhibitors. Hansotia, T., Baggio, L.L., Delmeire, D., Hinke, S.A., Yamada, Y., Tsukiyama, K., Seino, Y., Holst, J.J., Schuit, F., Drucker, D.J. Diabetes (2004) [Pubmed]
  27. Distinct effects of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 on insulin secretion and gut motility. Miki, T., Minami, K., Shinozaki, H., Matsumura, K., Saraya, A., Ikeda, H., Yamada, Y., Holst, J.J., Seino, S. Diabetes (2005) [Pubmed]
  28. Effects of gastric inhibitory polypeptide, vasoactive intestinal polypeptide and peptide histidine isoleucine on the secretion of hormones by isolated mouse pancreatic islets. Bailey, C.J., Wilkes, L.C., Conlon, J.M., Armstrong, P.H., Buchanan, K.D. J. Endocrinol. (1990) [Pubmed]
  29. Enhanced glucose-dependent insulinotropic polypeptide secretion and insulinotropic action in glucagon-like peptide 1 receptor -/- mice. Pederson, R.A., Satkunarajah, M., McIntosh, C.H., Scrocchi, L.A., Flamez, D., Schuit, F., Drucker, D.J., Wheeler, M.B. Diabetes (1998) [Pubmed]
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