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Gene Review

GIPR  -  gastric inhibitory polypeptide receptor

Homo sapiens

Synonyms: GIP-R, Gastric inhibitory polypeptide receptor, Glucose-dependent insulinotropic polypeptide receptor


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Disease relevance of GIPR


Psychiatry related information on GIPR

  • These data suggest that the GIP receptor plays a role in the regulation of locomotor activity and exploration [6].

High impact information on GIPR

  • However, a recent study using GIP receptor knockout mice suggests that inhibition of GIP signalling might be a new target for anti-obesity drugs [7].
  • GIP is a gastrointestinal peptide hormone of 42 amino acids that is released from duodenal endocrine K-cells after absorption of glucose or fat and exerts its effects by binding to its specific receptor, the GIP receptor [8].
  • By generating and characterizing mice with a targeted mutation of the GIP receptor gene, we have shown that GIP has not only an insulinotropic role, but also physiological roles on fat accumulation into adipose tissues and calcium accumulation into bone [8].
  • Similar protective effects were found with dispersed islet cells from C57BL/6 mice, but not with those from GIP receptor knock-out (GIPR(-/-)) mice [9].
  • GIP treatment reduced glucolipotoxicity-induced cell death in C57 BL/6 and Bax(-/-) islets, but not GIPR(-/-) mouse islets [9].

Chemical compound and disease context of GIPR


Biological context of GIPR


Anatomical context of GIPR


Associations of GIPR with chemical compounds

  • However, there was no trend toward low fasting or high postprandial cortisol in the other cases, suggesting that the presence of detectable GIPR alone, albeit with definite function in vitro, is not sufficient to cause clinically food-dependent CS [18].
  • Elimination of incretin receptor action in GIPR-/- or GLP-1R-/- mice produces only modest impairment in glucose homeostasis [19].
  • GIPR presumably acts, like the ACTH receptor (ACTHR), through the Gs protein/cyclic AMP/protein kinase A (PKA) pathway to stimulate steroidogenesis [10].
  • Mutation of the threonine at position 340 in the sixth transmembrane spanning domain to proline (T340P) led to agonist-independent constitutive activity and exhibited a four-fold increase in basal cAMP level as compared to the wild-type GIP-R [20].
  • Gastric inhibitory polypeptide receptor in hamster pancreatic beta cells. Direct cross-linking, solubilization and characterization as a glycoprotein [21].

Other interactions of GIPR


Analytical, diagnostic and therapeutic context of GIPR

GIPR in GH-secreting pituitary adenomas

  • By qPCR in GH-secreting pituitary adenomas and in normal pituitaries we show that nearly 25% of cases showed GIPR overexpression [26].
  • None of the GIPR-overexpressing somatotropinoma showed somatic mutation in the GNAS1 gene [26].
  • Immunostaining data showed both membrane and cytoplasmic reactivity. Different staining pattern could be observed among GIPR overexpressing somatotropinomas [26].
  • GIPR overexpression in associated with paradoxical increase of GH after OGTT [26] [27].


  1. Adrenocortical overexpression of gastric inhibitory polypeptide receptor underlies food-dependent Cushing's syndrome. N'Diaye, N., Tremblay, J., Hamet, P., De Herder, W.W., Lacroix, A. J. Clin. Endocrinol. Metab. (1998) [Pubmed]
  2. Asynchronous development of bilateral nodular adrenal hyperplasia in gastric inhibitory polypeptide-dependent cushing's syndrome. N'Diaye, N., Hamet, P., Tremblay, J., Boutin, J.M., Gaboury, L., Lacroix, A. J. Clin. Endocrinol. Metab. (1999) [Pubmed]
  3. Sp1/Sp3 binding is associated with cell-specific expression of the glucose-dependent insulinotropic polypeptide receptor gene. Boylan, M.O., Jepeal, L.I., Wolfe, M.M. Am. J. Physiol. Endocrinol. Metab. (2006) [Pubmed]
  4. Molecular cloning, functional expression, and signal transduction of the GIP-receptor cloned from a human insulinoma. Volz, A., Göke, R., Lankat-Buttgereit, B., Fehmann, H.C., Bode, H.P., Göke, B. FEBS Lett. (1995) [Pubmed]
  5. Food-dependent androgen and cortisol secretion by a gastric inhibitory polypeptide-receptor expressive adrenocortical adenoma leading to hirsutism and subclinical Cushing's syndrome: in vivo and in vitro studies. Tsagarakis, S., Tsigos, C., Vassiliou, V., Tsiotra, P., Pratsinis, H., Kletsas, D., Trivizas, P., Nikou, A., Mavromatis, T., Sotsiou, F., Raptis, S., Thalassinos, N. J. Clin. Endocrinol. Metab. (2001) [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. GIP or not GIP? That is the question. Kieffer, T.J. Trends Pharmacol. Sci. (2003) [Pubmed]
  8. Pancreatic and extrapancreatic effects of gastric inhibitory polypeptide. Yamada, Y., Miyawaki, K., Tsukiyama, K., Harada, N., Yamada, C., Seino, Y. Diabetes (2006) [Pubmed]
  9. 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]
  10. Expression of ACTH receptor pathway genes in glucose-dependent insulinotrophic peptide (GIP)-dependent Cushing's syndrome. Antonini, S.R., Baldacchino, V., Tremblay, J., Hamet, P., Lacroix, A. Clin. Endocrinol. (Oxf) (2006) [Pubmed]
  11. Aberrant receptor-mediated Cushing's syndrome. Bertagna, X., Groussin, L., Luton, J.P., Bertherat, J. Horm. Res. (2003) [Pubmed]
  12. Role of G protein-coupled receptor kinases in glucose-dependent insulinotropic polypeptide receptor signaling. Tseng, C.C., Zhang, X.Y. Endocrinology (2000) [Pubmed]
  13. Human gastric inhibitory polypeptide receptor: cloning of the gene (GIPR) and cDNA. Yamada, Y., Hayami, T., Nakamura, K., Kaisaki, P.J., Someya, Y., Wang, C.Z., Seino, S., Seino, Y. Genomics (1995) [Pubmed]
  14. Analysis of the putative regulatory region of the gastric inhibitory polypeptide receptor gene in food-dependent Cushing's syndrome. Antonini, S.R., N'Diaye, N., Baldacchino, V., Hamet, P., Tremblay, J., Lacroix, A. J. Steroid Biochem. Mol. Biol. (2004) [Pubmed]
  15. The Sp transcription factors are involved in the cellular expression of the human glucose-dependent insulinotropic polypeptide receptor gene and overexpressed in adrenals of patients with Cushing's syndrome. Baldacchino, V., Oble, S., Décarie, P.O., Bourdeau, I., Hamet, P., Tremblay, J., Lacroix, A. J. Mol. Endocrinol. (2005) [Pubmed]
  16. Glucose-dependent insulinotropic peptide stimulates thymidine incorporation in endothelial cells: role of endothelin-1. Ding, K.H., Zhong, Q., Isales, C.M. Am. J. Physiol. Endocrinol. Metab. (2003) [Pubmed]
  17. Improved stability, insulin-releasing activity and antidiabetic potential of two novel N-terminal analogues of gastric inhibitory polypeptide: N-acetyl-GIP and pGlu-GIP. O'Harte, F.P., Gault, V.A., Parker, J.C., Harriott, P., Mooney, M.H., Bailey, C.J., Flatt, P.R. Diabetologia (2002) [Pubmed]
  18. The aberrant expression of the gastric inhibitory polypeptide (GIP) receptor in adrenal hyperplasia: does chronic adrenocorticotropin exposure stimulate up-regulation of GIP receptors in Cushing's disease? Swords, F.M., Aylwin, S., Perry, L., Arola, J., Grossman, A.B., Monson, J.P., Clark, A.J. J. Clin. Endocrinol. Metab. (2005) [Pubmed]
  19. GIP and GLP-1 as incretin hormones: lessons from single and double incretin receptor knockout mice. Hansotia, T., Drucker, D.J. Regul. Pept. (2005) [Pubmed]
  20. A point mutation in the glucose-dependent insulinotropic peptide receptor confers constitutive activity. Tseng, C.C., Lin, L. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  21. Gastric inhibitory polypeptide receptor in hamster pancreatic beta cells. Direct cross-linking, solubilization and characterization as a glycoprotein. Amiranoff, B., Couvineau, A., Vauclin-Jacques, N., Laburthe, M. Eur. J. Biochem. (1986) [Pubmed]
  22. Role of regulator of G protein signaling in desensitization of the glucose-dependent insulinotropic peptide receptor. Tseng, C.C., Zhang, X.Y. Endocrinology (1998) [Pubmed]
  23. Cushing's syndrome due to a gastric inhibitory polypeptide-dependent adrenal adenoma: insights into hormonal control of adrenocortical tumorigenesis. Chabre, O., Liakos, P., Vivier, J., Chaffanjon, P., Labat-Moleur, F., Martinie, M., Bottari, S.P., Bachelot, I., Chambaz, E.M., Defaye, G., Feige, J.J. J. Clin. Endocrinol. Metab. (1998) [Pubmed]
  24. Assignment of the gastric inhibitory polypeptide receptor gene (GIPR) to chromosome bands 19q13.2-q13.3 by fluorescence in situ hybridization. Stoffel, M., Fernald, A.A., Le Beau, M.M., Bell, G.I. Genomics (1995) [Pubmed]
  25. Characterization of the cellular and metabolic effects of a novel enzyme-resistant antagonist of glucose-dependent insulinotropic polypeptide. Gault, V.A., O'Harte, F.P., Harriott, P., Flatt, P.R. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  26. The glucose-dependent insulinotropic polypeptide receptor is overexpressed amongst GNAS1 mutation-negative somatotropinomas and drives growth hormone (GH)-promoter activity in GH3 cells. Occhi, G., Losa, M., Albiger, N., Trivellin, G., Regazzo, D., Scanarini, M., Monteserin-Garcia, J.L., Fröhlich, B., Ferasin, S., Terreni, M.R., Fassina, A., Vitiello, L., Stalla, G., Mantero, F., Scaroni, C. J. Neuroendocrinol. (2011) [Pubmed]
  27. Glucose-dependent insulinotropic polypeptide induced growth hormone secretion in acromegaly. Umahara, M., Okada, S., Ohshima, K., Mori, M. Endocr. J. (2003) [Pubmed]
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