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Gene Review

Gip  -  gastric inhibitory polypeptide

Rattus norvegicus

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


Psychiatry related information on Gip

  • These data suggest that dietary glucose or fat stimulates GIP synthesis and secretion, and that food deprivation causes a decrease in GIP synthesis and secretion [6].

High impact information on Gip


Chemical compound and disease context of Gip

  • In addition, we examined the effect of amylin on GIP-induced insulin release in pancreata from rats pretreated with pertussis toxin, an agent which inactivates certain Gi proteins coupled to adenylate cyclase [10].
  • Pretreatment of cells with 200 ng/ml pertussis toxin for 3 h, or incubation with the ATP-sensitive K+ channel blocker disopyramide (200 microM), prevented the inhibition by galanin of bombesin- and GIP-stimulated GLP-1 secretion [11].

Biological context of Gip


Anatomical context of Gip


Associations of Gip with chemical compounds

  • In conclusion, these data show that stimulation of glucagon, GLP-I, and GIP receptors in rat beta-cells causes cAMP production required for insulin release, while adenylate cyclase in alpha-cells is positively regulated by GIP [17].
  • GIP stimulated adenosine 3', 5'-cyclic monophosphate (cAMP) production in LGIPR2 cells, which was first detected after 1 h of stimulation, reached maximum level at 4 h, and returned to basal concentrations by 16 h [18].
  • Finally, we have shown that GIP regulation of the ERK1/2 module is via Rap1 but does not involve Gbetagamma subunits nor Src tyrosine kinase, and we propose that cAMP-based regulation occurs via B-Raf in both CHO-K1 and beta-cells [19].
  • 2. Glucagon and GIP were ineffective inhibitors of basal and pentagastrin-stimulated secretion [20].
  • Rat GIP differs from the human hormone by two amino acid substitutions: arginine for histidine at position 18 and leucine for isoleucine at position 40 [21].

Regulatory relationships of Gip

  • Treatment with GIPR Ab (1 microg/g BW) blocked the potentiation of glucose-stimulated insulin secretion by GIP (60 pmol) but not glucagon-like peptide-1 (GLP-1, 60 pmol) in anesthetized rats [22].
  • EC50 values of GLP-I- and GIP-induced cAMP formation were comparable (0.2 nmol/l) and 45-fold lower than the EC50 of glucagon (9 nmol/l) [17].
  • GIP significantly inhibited carbachol-stimulated gastrin release into the culture media at all concentrations examined [23].
  • It is concluded that DPP IV may be a primary inactivating enzyme of both GIP and tGLP-1 in vivo [24].
  • Neither insulin- nor glucose-dependent insulinotropic polypeptide-stimulated lipoprotein lipase was modified by the presence of the antibiotic actinomycin-D in the incubation medium, indicating that these two hormones exert their actions on the pre-existing cellular pool of lipoprotein lipase [25].

Other interactions of Gip

  • Glucagon-like peptide I and glucose-dependent insulinotropic polypeptide stimulate Ca2+-induced secretion in rat alpha-cells by a protein kinase A-mediated mechanism [13].
  • Heterologous desensitization of GLP-1-dependent insulin secretion by pretreatment with GIP, however, was not inhibited by calcium/calmodulin-dependent enzymes (using KN-62 and FK 506), but only by suppressing the cAMP/PKA signalling pathway using Rp-8-Br-cAMPS [26].
  • By using either the CaM kinase II inhibitor KN-62, the calcineurin inhibitor FK 506 or the protein kinase A (PKA) inhibitor Rp-8-Br-cAMPS, the GIP-mediated Galphai2 mRNA increase was fully reversed [26].
  • Reduction of the luminal pH to 2 resulted in an inhibition of BLI secretion by GIP while gastrin release was abolished and somatostatin remained unaffected compared to luminal pH 7 [27].
  • On the other hand, infusion of naloxone 10(-6) M attenuates the inhibitory effect of N/OFQ 10(-6) M significantly (-21+/-6%; p<0.05 vs. GIP and N/OFQ).Thus, N/OFQ is an inhibitor of gastric somatostatin secretion [28].

Analytical, diagnostic and therapeutic context of Gip


  1. Postprandial stimulation of insulin release by glucose-dependent insulinotropic polypeptide (GIP). Effect of a specific glucose-dependent insulinotropic polypeptide receptor antagonist in the rat. Tseng, C.C., Kieffer, T.J., Jarboe, L.A., Usdin, T.B., Wolfe, M.M. J. Clin. Invest. (1996) [Pubmed]
  2. Functional expression of the rat pancreatic islet glucose-dependent insulinotropic polypeptide receptor: ligand binding and intracellular signaling properties. Wheeler, M.B., Gelling, R.W., McIntosh, C.H., Georgiou, J., Brown, J.C., Pederson, R.A. Endocrinology (1995) [Pubmed]
  3. Identification of a bioactive domain in the amino-terminus of glucose-dependent insulinotropic polypeptide (GIP). Hinke, S.A., Manhart, S., Pamir, N., Demuth, H., W Gelling, R., Pederson, R.A., McIntosh, C.H. Biochim. Biophys. Acta (2001) [Pubmed]
  4. Effects of cholecystokinin, gastric inhibitory polypeptide, and secretin on insulin and glucagon secretion in rats. Szecówka, J., Lins, P.E., Efendić, S. Endocrinology (1982) [Pubmed]
  5. Binding specificity and signal transduction of receptors for glucagon-like peptide-1(7-36)amide and gastric inhibitory polypeptide on RINm5F insulinoma cells. Gallwitz, B., Witt, M., Fölsch, U.R., Creutzfeldt, W., Schmidt, W.E. J. Mol. Endocrinol. (1993) [Pubmed]
  6. Dietary regulation of glucose-dependent insulinotropic peptide (GIP) gene expression in rat small intestine. Higashimoto, Y., Opara, E.C., Liddle, R.A. Comp. Biochem. Physiol. C, Pharmacol. Toxicol. Endocrinol. (1995) [Pubmed]
  7. Release of gastric inhibitory polypeptide (GIP) by intraduodenal acidification in rats and humans and abolishment of the incretin effect of acid by GIP-antiserum in rats. Ebert, R., Illmer, K., Creutzfeldt, W. Gastroenterology (1979) [Pubmed]
  8. Structure-activity relationships of gastrointestinal hormones: motilin, GIP, and [27-TYR]CCK-PZ. Yajima, H., Kai, Y., Ogawa, H., Kubota, M., Mori, Y. Gastroenterology (1977) [Pubmed]
  9. Glucose-dependent insulinotropic peptide: structure of the precursor and tissue-specific expression in rat. Tseng, C.C., Jarboe, L.A., Landau, S.B., Williams, E.K., Wolfe, M.M. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  10. Amylin (islet amyloid polypeptide) inhibition of insulin release in the perfused rat pancreas: implication of the adenylate cyclase/cAMP system. Silvestre, R.A., Salas, M., García-Hermida, O., Fontela, T., Dégano, P., Marco, J. Regul. Pept. (1994) [Pubmed]
  11. Galanin inhibits glucagon-like peptide-1 secretion through pertussis toxin-sensitive G protein and ATP-dependent potassium channels in rat ileal L-cells. Saïfia, S., Chevrier, A.M., Bosshard, A., Cuber, J.C., Chayvialle, J.A., Abello, J. J. Endocrinol. (1998) [Pubmed]
  12. Defective glucose-dependent insulinotropic polypeptide receptor expression in diabetic fatty Zucker rats. Lynn, F.C., Pamir, N., Ng, E.H., McIntosh, C.H., Kieffer, T.J., Pederson, R.A. Diabetes (2001) [Pubmed]
  13. Glucagon-like peptide I and glucose-dependent insulinotropic polypeptide stimulate Ca2+-induced secretion in rat alpha-cells by a protein kinase A-mediated mechanism. Ding, W.G., Renström, E., Rorsman, P., Buschard, K., Gromada, J. Diabetes (1997) [Pubmed]
  14. Functional GIP receptors are present on adipocytes. Yip, R.G., Boylan, M.O., Kieffer, T.J., Wolfe, M.M. Endocrinology (1998) [Pubmed]
  15. Receptor gene expression of glucagon-like peptide-1, but not glucose-dependent insulinotropic polypeptide, in rat nodose ganglion cells. Nakagawa, A., Satake, H., Nakabayashi, H., Nishizawa, M., Furuya, K., Nakano, S., Kigoshi, T., Nakayama, K., Uchida, K. Autonomic neuroscience : basic & clinical. (2004) [Pubmed]
  16. Gastric inhibitory polypeptide receptor, a member of the secretin-vasoactive intestinal peptide receptor family, is widely distributed in peripheral organs and the brain. Usdin, T.B., Mezey, E., Button, D.C., Brownstein, M.J., Bonner, T.I. Endocrinology (1993) [Pubmed]
  17. Expression and functional activity of glucagon, glucagon-like peptide I, and glucose-dependent insulinotropic peptide receptors in rat pancreatic islet cells. Moens, K., Heimberg, H., Flamez, D., Huypens, P., Quartier, E., Ling, Z., Pipeleers, D., Gremlich, S., Thorens, B., Schuit, F. Diabetes (1996) [Pubmed]
  18. Chronic desensitization of the glucose-dependent insulinotropic polypeptide receptor in diabetic rats. Tseng, C.C., Boylan, M.O., Jarboe, L.A., Usdin, T.B., Wolfe, M.M. Am. J. Physiol. (1996) [Pubmed]
  19. Glucose-dependent insulinotropic polypeptide activates the Raf-Mek1/2-ERK1/2 module via a cyclic AMP/cAMP-dependent protein kinase/Rap1-mediated pathway. Ehses, J.A., Pelech, S.L., Pederson, R.A., McIntosh, C.H. J. Biol. Chem. (2002) [Pubmed]
  20. Effects of various gastrointestinal peptides on parietal cells and endocrine cells in the oxyntic mucosa of rat stomach. El Munshid, H.A., Håkanson, R., Liedberg, G., Sundler, F. J. Physiol. (Lond.) (1980) [Pubmed]
  21. Molecular cloning of rat glucose-dependent insulinotropic peptide (GIP). Higashimoto, Y., Simchock, J., Liddle, R.A. Biochim. Biophys. Acta (1992) [Pubmed]
  22. Glucose-dependent insulinotropic polypeptide confers early phase insulin release to oral glucose in rats: demonstration by a receptor antagonist. Lewis, J.T., Dayanandan, B., Habener, J.F., Kieffer, T.J. Endocrinology (2000) [Pubmed]
  23. Inhibition of gastrin release by gastric inhibitory peptide mediated by somatostatin. Wolfe, M.M., Reel, G.M. Am. J. Physiol. (1986) [Pubmed]
  24. Degradation of glucose-dependent insulinotropic polypeptide and truncated glucagon-like peptide 1 in vitro and in vivo by dipeptidyl peptidase IV. Kieffer, T.J., McIntosh, C.H., Pederson, R.A. Endocrinology (1995) [Pubmed]
  25. Investigations into the actions of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1(7-36)amide on lipoprotein lipase activity in explants of rat adipose tissue. Knapper, J.M., Puddicombe, S.M., Morgan, L.M., Fletcher, J.M. J. Nutr. (1995) [Pubmed]
  26. Heterologous desensitization of insulin secretion by GIP (glucose-dependent insulinotropic peptide) in INS-1 cells: the significance of Galphai2 and investigations on the mechanism involved. Rucha, A., Verspohl, E.J. Cell Biochem. Funct. (2005) [Pubmed]
  27. Release of bombesin-like immunoreactivity from the isolated perfused rat stomach. Schusdziarra, V., Bender, H., Pfeiffer, E.F. Regul. Pept. (1983) [Pubmed]
  28. Inhibitory effect of nociceptin on somatostatin secretion of the isolated perfused rat stomach. Lippl, F., Schusdziarra, V., Huepgens, K., Allescher, H.D. Regul. Pept. (2002) [Pubmed]
  29. Gastric inhibitory polypeptide (GIP) binding sites in rat brain. Kaplan, A.M., Vigna, S.R. Peptides (1994) [Pubmed]
  30. Gastric inhibitory polypeptide and glucagon-like peptide-1(7-36) amide exert similar effects on somatostatin secretion but opposite effects on gastrin secretion from the rat stomach. Jia, X., Brown, J.C., Kwok, Y.N., Pederson, R.A., McIntosh, C.H. Can. J. Physiol. Pharmacol. (1994) [Pubmed]
  31. Characterization of the carboxyl-terminal domain of the rat glucose-dependent insulinotropic polypeptide (GIP) receptor. A role for serines 426 and 427 in regulating the rate of internalization. Wheeler, M.B., Gelling, R.W., Hinke, S.A., Tu, B., Pederson, R.A., Lynn, F., Ehses, J., McIntosh, C.H. J. Biol. Chem. (1999) [Pubmed]
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