The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

GIP  -  gastric inhibitory polypeptide

Homo sapiens

Synonyms: Gastric inhibitory polypeptide, Glucose-dependent insulinotropic polypeptide, Incretin hormone
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of GIP

  • The insulinotropic effect of GLP-1 is maintained in patients with Type II (non-insulin-dependent) diabetes mellitus, whereas, for unknown reasons, the effect of GIP is diminished or lacking [1].
  • METHODS: Ten healthy subjects (9 men, 1 woman; age 33+/-11; BMI 26.8+/-2.2 kg/m(2)) received three different doses of intravenous GIP (7, 20, and 60 pmol/kg body weight) and placebo [2].
  • CONCLUSION: These studies exclude both GIP and GLP-1 as key mediators for the immediate reduction in bone resorption seen after a meal [3].
  • We conclude that the GIPR overexpression and its coupling to steroidogenesis underlie GIP-dependent Cushing's syndrome [4].
  • We conclude that GIP-dependent nodular hyperplasia can progress in an asynchronous manner and that GIPR overexpression is an early event in this syndrome [5].

Psychiatry related information on GIP


High impact information on GIP

  • Cell suspensions of adrenal tissue from the patient produced more cortisol when stimulated by GIP than when stimulated by corticotropin [11].
  • The development of aberrant adrenal sensitivity to GIP can result in food-dependent adrenal hyperplasia and therefore in Cushing's syndrome [12].
  • In contrast, adrenal cells from normal adults and fetuses or patients with cortisol-producting or aldosterone-producing adenomas responded to corticotropin but not to GIP [11].
  • These include ectopic receptors for gastric inhibitory polypeptide (GIP), beta-adrenergic agonists, or LH/hCG; a similar outcome can result from altered activity of eutopic receptors, such as those for vasopressin (V1-AVPR), serotonin (5-HT4), or possibly leptin [13].
  • The targeting of proteins to mitochondria involves the recognition of the precursor proteins by receptors on the mitochondrial surface followed by insertion of the precursors into the outer membrane at the general insertion site GIP [14].

Chemical compound and disease context of GIP


Biological context of GIP


Anatomical context of GIP

  • Complementary DNA clones encoding human GIP were isolated from a library prepared with RNA from duodenum [19].
  • Cultured subcutaneous human adipocytes showed similar responses to GIP but with greater sensitivity [20].
  • AIMS/HYPOTHESIS: In the isolated perfused pancreas, gastric inhibitory polypeptide (GIP) has been shown to enhance glucagon secretion at basal glucose concentrations, but in healthy humans no glucagonotropic effect of GIP has yet been reported [2].
  • RESULTS: Human islet cells express transcripts encoding glucagon, GLP-1 and GIP receptors [22].
  • In conclusion, amino acid variants in the GIP receptor are not associated with random Type II diabetes in patients of Danish Caucasian origin or with altered GIP binding and GIP-induced cAMP production when stably transfected in Chinese hamster fibroblasts [1].

Associations of GIP with chemical compounds

  • Gastric inhibitory polypeptide (GIP) is a 42-amino acid hormone that stimulates insulin secretion in the presence of glucose [19].
  • GIP is released from the precursor by processing at single arginine residues [19].
  • The GIP moiety is flanked by polypeptide segments of 51 and 60 amino acids at its NH2 and COOH termini, respectively [19].
  • Parenteral administration of GIP and GLP-1 did not result in a reduction of the s-CTX level, whereas GLP-2 caused a statistically significant and dose-dependent reduction in the s-CTX level from baseline compared with placebo (p < 0.05) [3].
  • Three months after surgery, fasting plasma ACTH and cortisol were suppressed, but cortisol increased 3.6-fold after oral glucose, whereas ACTH remained suppressed; this was inhibited by octreotide pretreatment, suggesting that cortisol secretion by the left adrenal is also GIP dependent [5].

Physical interactions of GIP


Regulatory relationships of GIP

  • RESULTS: Gastric inhibitory polypeptide dose-dependently stimulated glucagon secretion ( p=0.019) with a maximal increment after 10 min [2].
  • We studied 9.0kb upstream and 1.3kb downstream of the GIPR gene putative promoter (pProm) by sequencing leukocyte DNA from controls and from adrenal tissues of GIP- and non-GIP-dependent CS patients [24].
  • CCK-8, CCK-33, and GIP (100 pmol/kg) all potentiated the meal-induced plasma responses of insulin and PP, whereas plasma levels of glucagon after the meal were not affected [25].
  • In contrast, RGS2 expression inhibited the GIP-induced cAMP response by 50%, a response similar to that of cells desensitized by preincubation with 10(-7) M GIP [26].
  • GIP-stimulated cAMP generation in control cells and in those coexpressing RGS1, -3, and -4 displayed a dose-dependent increase 10 min after GIP treatment [26].

Other interactions of GIP

  • Therefore, we studied the effect of GIP on glucagon secretion under normoglycaemic conditions [2].
  • New alternative spliced isoforms of the GIPR were found, but are identical in GIP-dependent and normal adrenal tissues [4].
  • These results suggest a potential role for GRK2/beta-arrestin-1 system in modulating GIP-mediated insulin secretion in pancreatic islet cells [27].
  • GIP maps distal to NGFR with an estimated distance of 250 kb [28].
  • Infusion of the CCK receptor antagonist only slightly increased postprandial peak plasma glucose, insulin and C-peptide levels, whereas GIP and neurotensin levels were not significantly influenced [29].

Analytical, diagnostic and therapeutic context of GIP

  • The finding of an association between homozygosity for the codon 354 variant and reduced fasting and post oral glucose tolerance test (OGTT) serum C-peptide concentrations, however, calls for further investigations and could suggest that GIP even in the fasting state regulates the beta-cell secretory response [1].
  • Venous blood samples were drawn over 30 min for glucagon and GIP concentrations (specific radioimmunoassays) [2].
  • METHODS: Expression of the glucagon, GLP-1 and GIP receptors in human islets was investigated by northern blots and reverse transcription-polymerase chain reaction analysis [22].
  • Collectively these data demonstrate that (Pro(3))GIP is a novel and potent enzyme-resistant GIP receptor antagonist capable of blocking the ability of native GIP to increase cAMP, stimulate insulin secretion, and improve glucose homeostasis in a commonly employed animal model of type 2 diabetes [30].
  • Plasma glucose, GIP, GLP-1, insulin and paracetamol concentrations were measured before and after a 100 g oral carhohydrate load containing 1.5 g of paracetamol for 6 h during intravenous infusion of either glucagon or saline [31].


  1. Discovery of amino acid variants in the human glucose-dependent insulinotropic polypeptide (GIP) receptor: the impact on the pancreatic beta cell responses and functional expression studies in Chinese hamster fibroblast cells. Almind, K., Ambye, L., Urhammer, S.A., Hansen, T., Echwald, S.M., Holst, J.J., Gromada, J., Thorens, B., Pedersen, O. Diabetologia (1998) [Pubmed]
  2. Gastric inhibitory polypeptide (GIP) dose-dependently stimulates glucagon secretion in healthy human subjects at euglycaemia. Meier, J.J., Gallwitz, B., Siepmann, N., Holst, J.J., Deacon, C.F., Schmidt, W.E., Nauck, M.A. Diabetologia (2003) [Pubmed]
  3. Role of gastrointestinal hormones in postprandial reduction of bone resorption. Henriksen, D.B., Alexandersen, P., Bjarnason, N.H., Vilsbøll, T., Hartmann, B., Henriksen, E.E., Byrjalsen, I., Krarup, T., Holst, J.J., Christiansen, C. J. Bone Miner. Res. (2003) [Pubmed]
  4. 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]
  5. 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]
  6. Cholecystokinin, glucose dependent insulinotropic peptide and glucagon-like peptide 1 secretion in children with anorexia nervosa and simple obesity. Tomasik, P.J., Sztefko, K., Starzyk, J. Journal of pediatric endocrinology & metabolism : JPEM. (2004) [Pubmed]
  7. Circadian rhythm of gastric inhibitory polypeptide (GIP) in man. Salera, M., Giacomoni, P., Pironi, L., Ustra, C., Capelli, M., Giorgi, A., Miglioli, M., Barbara, L. Metab. Clin. Exp. (1983) [Pubmed]
  8. The effect of dietary modification and hyperglycaemia on gastric emptying and gastric inhibitory polypeptide (GIP) secretion. Morgan, L.M., Tredger, J.A., Hampton, S.M., French, A.P., Peake, J.C., Marks, V. Br. J. Nutr. (1988) [Pubmed]
  9. Bright light therapy and melatonin in motor restless behaviour in dementia: a placebo-controlled study. Haffmans, P.M., Sival, R.C., Lucius, S.A., Cats, Q., van Gelder, L. International journal of geriatric psychiatry. (2001) [Pubmed]
  10. Down and drowsy? Do apathetic nursing home residents experience low quality of life? Gerritsen, D.L., Jongenelis, K., Steverink, N., Ooms, M.E., Ribbe, M.W. Aging & mental health. (2005) [Pubmed]
  11. Gastric inhibitory polypeptide-dependent cortisol hypersecretion--a new cause of Cushing's syndrome. Lacroix, A., Bolté, E., Tremblay, J., Dupré, J., Poitras, P., Fournier, H., Garon, J., Garrel, D., Bayard, F., Taillefer, R. N. Engl. J. Med. (1992) [Pubmed]
  12. Food-dependent Cushing's syndrome mediated by aberrant adrenal sensitivity to gastric inhibitory polypeptide. Reznik, Y., Allali-Zerah, V., Chayvialle, J.A., Leroyer, R., Leymarie, P., Travert, G., Lebrethon, M.C., Budi, I., Balliere, A.M., Mahoudeau, J. N. Engl. J. Med. (1992) [Pubmed]
  13. Ectopic and abnormal hormone receptors in adrenal Cushing's syndrome. Lacroix, A., Ndiaye, N., Tremblay, J., Hamet, P. Endocr. Rev. (2001) [Pubmed]
  14. Targeting of the master receptor MOM19 to mitochondria. Schneider, H., Söllner, T., Dietmeier, K., Eckerskorn, C., Lottspeich, F., Trülzsch, B., Neupert, W., Pfanner, N. Science (1991) [Pubmed]
  15. Gastric inhibitory polypeptide and glucagon-like peptide-1 in the pathogenesis of type 2 diabetes. Nauck, M.A., Baller, B., Meier, J.J. Diabetes (2004) [Pubmed]
  16. The diversity of abnormal hormone receptors in adrenal Cushing's syndrome allows novel pharmacological therapies. Lacroix, A., N'Diaye, N., Mircescu, H., Tremblay, J., Hamet, P. Braz. J. Med. Biol. Res. (2000) [Pubmed]
  17. Triphenyltin impairs a protein kinase A (PKA)-dependent increase of cytosolic Na(+) and Ca(2+) and PKA-independent increase of cytosolic Ca(2+) associated with insulin secretion in hamster pancreatic beta-cells. Miura, Y., Matsui, H. Toxicol. Appl. Pharmacol. (2006) [Pubmed]
  18. Evidence of functional gastric inhibitory polypeptide (GIP) receptors in human insulinoma. Binding of synthetic human GIP 1-31 and activation of adenylate cyclase. Maletti, M., Altman, J.J., Hoa, D.H., Carlquist, M., Rosselin, G. Diabetes (1987) [Pubmed]
  19. Sequence of an intestinal cDNA encoding human gastric inhibitory polypeptide precursor. Takeda, J., Seino, Y., Tanaka, K., Fukumoto, H., Kayano, T., Takahashi, H., Mitani, T., Kurono, M., Suzuki, T., Tobe, T. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  20. Activation of Lipoprotein Lipase by Glucose-dependent Insulinotropic Polypeptide in Adipocytes: A ROLE FOR A PROTEIN KINASE B, LKB1, AND AMP-ACTIVATED PROTEIN KINASE CASCADE. Kim, S.J., Nian, C., McIntosh, C.H. J. Biol. Chem. (2007) [Pubmed]
  21. A novel mechanism for the suppression of a voltage-gated potassium channel by glucose-dependent insulinotropic polypeptide: protein kinase A-dependent endocytosis. Kim, S.J., Choi, W.S., Han, J.S., Warnock, G., Fedida, D., McIntosh, C.H. J. Biol. Chem. (2005) [Pubmed]
  22. Glucagon receptors on human islet cells contribute to glucose competence of insulin release. Huypens, P., Ling, Z., Pipeleers, D., Schuit, F. Diabetologia (2000) [Pubmed]
  23. Survey of functional activities of alpha-fetoprotein derived growth inhibitory peptides: review and prospects. Mizejewskia, G.J., Butterstein, G. Curr. Protein Pept. Sci. (2006) [Pubmed]
  24. 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]
  25. Effects of cholecystokinin (CCK)-8, CCK-33, and gastric inhibitory polypeptide (GIP) on basal and meal-stimulated pancreatic hormone secretion in man. Ahrén, B., Pettersson, M., Uvnäs-Moberg, K., Gutniak, M., Efendic, S. Diabetes Res. Clin. Pract. (1991) [Pubmed]
  26. 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]
  27. Role of G protein-coupled receptor kinases in glucose-dependent insulinotropic polypeptide receptor signaling. Tseng, C.C., Zhang, X.Y. Endocrinology (2000) [Pubmed]
  28. Localization of glucose-dependent insulinotropic polypeptide (GIP) to a gene cluster on chromosome 17q. Lewis, T.B., Saenz, M., O'Connell, P., Leach, R.J. Genomics (1994) [Pubmed]
  29. Cholecystokinin receptor antagonist loxiglumide modulates plasma levels of gastro-entero-pancreatic hormones in man. Feedback control of cholecystokinin and gastrin secretion. Schmidt, W.E., Creutzfeldt, W., Höcker, M., Nustede, R., Choudhury, A.R., Schleser, A., Rovati, L.C., Fölsch, U.R. Eur. J. Clin. Invest. (1991) [Pubmed]
  30. 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]
  31. Effect of glucagon on carbohydrate-mediated secretion of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (7-36 amide) (GLP-1). Ranganath, L., Schaper, F., Gama, R., Morgan, L., Wright, J., Teale, D., Marks, V. Diabetes Metab. Res. Rev. (1999) [Pubmed]
WikiGenes - Universities