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Gene Review

Gipr  -  gastric inhibitory polypeptide receptor

Mus musculus

Synonyms: GIP-R, Gastric inhibitory polypeptide receptor, Glucose-dependent insulinotropic polypeptide receptor, Gm1081, Gm160, ...
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Disease relevance of Gipr

  • The Gipr(-/-) mice had a lower respiratory quotient and used fat as the preferred energy substrate, and were thus resistant to obesity [1].
  • No evidence was found for GIP receptor desensitization and the metabolic effects of N-AcGIP(LysPAL(37)) were independent of any change in feeding or body weight [2].

Psychiatry related information on Gipr

  • These data suggest that the GIP receptor plays a role in the regulation of locomotor activity and exploration [3].

High impact information on Gipr


Biological context of Gipr

  • 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 [7].
  • In conclusion, GIPR(-/-) mice exhibit altered islet structure and topography and increased islet sensitivity to GLP-1 despite a decrease in pancreatic insulin content and gene expression [8].
  • Further, GIPR-/- mice had earlier age-related changes than wild-type mice in body composition, including bone mass, lean body mass, and fat percentage [9].
  • The GIPR-/- mice showed a decreased bone size, lower bone mass, altered bone microarchitecture and biomechanical properties, and altered parameters for bone turnover, especially in bone formation [9].
  • In the present study, we investigated the role of GIP in modulating bone turnover, by evaluating serum markers of bone turnover, bone density, bone morphology, and changes in biomechanical bone strength over time (one to five months) in GIP receptor knockout mice (GIPR-/- mice) [9].

Anatomical context of Gipr


Associations of Gipr with chemical compounds

  • GIP-R ablation also significantly lowered overall plasma glucose (1.4-fold; P < 0.05) and insulin (1.5-fold; P < 0.05) responses to feeding [7].
  • These data demonstrate that acylation of Lys(16) with palmitic acid in (Pro(3))GIP does not improve its biological effectiveness as a GIP receptor antagonist [14].

Regulatory relationships of Gipr

  • In vitro studies demonstrated that GIP analogues retained their ability to activate the GIP receptor through production of cAMP and to stimulate insulin secretion [15].

Other interactions of Gipr

  • These studies highlight a role for GIP in obesity-related glucose intolerance and emphasize the potential of specific GIP-R antagonists as a new class of drugs for the alleviation of insulin resistance and treatment of type 2 diabetes [7].
  • In contrast, GIPR Ab had no effect on glucose excursion or insulin secretion, after ip glucose challenge, in +/+ or GLP-1R-/- mice [16].
  • METHODS: Double-knockout mice were generated by intercrossing Kir6.2-knockout mice with GIP receptor-knockout mice [17].
  • GIP receptor messenger RNA was detected by RT-PCR and RNase protection assay [18].
  • The glucose-dependent insulinotropic peptide receptor (GIP-R) is a member of G-protein-coupled, seven transmembrane-spanning receptors [19].

Analytical, diagnostic and therapeutic context of Gipr


  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. A novel, long-acting agonist of glucose-dependent insulinotropic polypeptide suitable for once-daily administration in type 2 diabetes. Irwin, N., Green, B.D., Mooney, M.H., Greer, B., Harriott, P., Bailey, C.J., Gault, V.A., O'Harte, F.P., Flatt, P.R. J. Pharmacol. Exp. Ther. (2005) [Pubmed]
  3. 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]
  4. Gluco-incretins control insulin secretion at multiple levels as revealed in mice lacking GLP-1 and GIP receptors. Preitner, F., Ibberson, M., Franklin, I., Binnert, C., Pende, M., Gjinovci, A., Hansotia, T., Drucker, D.J., Wollheim, C., Burcelin, R., Thorens, B. J. Clin. Invest. (2004) [Pubmed]
  5. 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]
  6. 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]
  7. 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]
  8. 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]
  9. 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]
  10. Effects on glucose homeostasis and insulin secretion of long term activation of the glucose-dependent insulinotropic polypeptide (GIP) receptor by N-AcGIP(LysPAL37) in normal mice. Irwin, N., Green, B.D., Gault, V.A., Cassidy, R.S., O'Harte, F.P., Harriott, P., Flatt, P.R. Peptides (2006) [Pubmed]
  11. Glucose-dependent insulinotropic polypeptide is expressed in adult hippocampus and induces progenitor cell proliferation. Nyberg, J., Anderson, M.F., Meister, B., Alborn, A.M., Ström, A.K., Brederlau, A., Illerskog, A.C., Nilsson, O., Kieffer, T.J., Hietala, M.A., Ricksten, A., Eriksson, P.S. J. Neurosci. (2005) [Pubmed]
  12. Degradation, insulin secretion, and antihyperglycemic actions of two palmitate-derivitized N-terminal pyroglutamyl analogues of glucose-dependent insulinotropic polypeptide. Irwin, N., Green, B.D., Gault, V.A., Greer, B., Harriott, P., Bailey, C.J., Flatt, P.R., O'Harte, F.P. J. Med. Chem. (2005) [Pubmed]
  13. 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]
  14. Characterisation and glucoregulatory actions of a novel acylated form of the (Pro(3))GIP receptor antagonist in type 2 diabetes. Gault, V.A., Hunter, K., Irwin, N., Greer, B., Green, B.D., Harriott, P., O'harte, F.P., Flatt, P.R. Biol. Chem. (2007) [Pubmed]
  15. 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]
  16. Glucagon-like peptide-1, but not glucose-dependent insulinotropic peptide, regulates fasting glycemia and nonenteral glucose clearance in mice. Baggio, L., Kieffer, T.J., Drucker, D.J. Endocrinology (2000) [Pubmed]
  17. Gastric inhibitory polypeptide is the major insulinotropic factor in K(ATP) null mice. Tsukiyama, K., Yamada, Y., Miyawaki, K., Hamasaki, A., Nagashima, K., Hosokawa, M., Fujimoto, S., Takahashi, A., Toyoda, K., Toyokuni, S., Oiso, Y., Seino, Y. Eur. J. Endocrinol. (2004) [Pubmed]
  18. Glucose-dependent insulinotropic polypeptide stimulation of lipolysis in differentiated 3T3-L1 cells: wortmannin-sensitive inhibition by insulin. McIntosh, C.H., Bremsak, I., Lynn, F.C., Gill, R., Hinke, S.A., Gelling, R., Nian, C., McKnight, G., Jaspers, S., Pederson, R.A. Endocrinology (1999) [Pubmed]
  19. The cysteine of the cytoplasmic tail of glucose-dependent insulinotropic peptide receptor mediates its chronic desensitization and down-regulation. Tseng, C.C., Zhang, X.Y. Mol. Cell. Endocrinol. (1998) [Pubmed]
  20. Ectopic expression of the gastric inhibitory polypeptide receptor gene is a sufficient genetic event to induce benign adrenocortical tumor in a xenotransplantation model. Mazzuco, T.L., Chabre, O., Sturm, N., Feige, J.J., Thomas, M. Endocrinology (2006) [Pubmed]
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