Gastroenterology
Volume 138, Issue 5 , Pages 1966-1975.e1 , May 2010

Glucose-Dependent Insulinotropic Polypeptide Is Expressed in Pancreatic Islet α-Cells and Promotes Insulin Secretion

  • Yukihiro Fujita

      Affiliations

    • Laboratory of Molecular and Cellular Medicine, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada
    • Department of Cellular & Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada
  • ,
  • Rhonda D. Wideman

      Affiliations

    • Laboratory of Molecular and Cellular Medicine, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada
    • Department of Cellular & Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada
  • ,
  • Ali Asadi

      Affiliations

    • Laboratory of Molecular and Cellular Medicine, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada
    • Department of Cellular & Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada
  • ,
  • Gary K. Yang

      Affiliations

    • Laboratory of Molecular and Cellular Medicine, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada
    • Department of Cellular & Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada
  • ,
  • Robert Baker

      Affiliations

    • Laboratory of Molecular and Cellular Medicine, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada
    • Department of Cellular & Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada
  • ,
  • Travis Webber

      Affiliations

    • Laboratory of Molecular and Cellular Medicine, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada
    • Department of Cellular & Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada
  • ,
  • Tianjiao Zhang

      Affiliations

    • Laboratory of Molecular and Cellular Medicine, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada
    • Department of Cellular & Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada
  • ,
  • Rennian Wang

      Affiliations

    • Department of Physiology and Pharmacology, Children's Health Research Institute, University of Western Ontario, London, Ontario, Canada
  • ,
  • Ziliang Ao

      Affiliations

    • Department of Surgery, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada
  • ,
  • Garth L. Warnock

      Affiliations

    • Department of Surgery, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada
  • ,
  • Yin Nam Kwok

      Affiliations

    • Department of Cellular & Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada
  • ,
  • Timothy J. Kieffer

      Affiliations

    • Laboratory of Molecular and Cellular Medicine, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada
    • Department of Cellular & Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada
    • Department of Surgery, Life Sciences Institute, University of British Columbia, Vancouver, British Columbia, Canada
    • Corresponding Author InformationReprint requests Address requests for reprints to: Timothy J. Kieffer, PhD, 2350 Health Sciences Mall, Vancouver, British Columbia, V6T 1Z3 Canada. fax: (604) 822-2316

Received 4 December 2008 ,Accepted 27 January 2010.

References 

  1. Pederson RA, Schubert HE, Brown JC. Gastric inhibitory polypeptide (Its physiologic release and insulinotropic action in the dog). Diabetes. 1975;24:1050–1056
  2. Pederson RA, Brown JC. The insulinotropic action of gastric inhibitory polypeptide in the perfused isolated rat pancreas. Endocrinology. 1976;99:780–785
  3. Brown JC, Dryburgh JR. A gastric inhibitory polypeptide (II. The complete amino acid sequence). Can J Biochem. 1971;49:867–872
  4. Kieffer TJ, Habener JF. The glucagon-like peptides. Endocr Rev. 1999;20:876–913
  5. Kolligs F, Fehmann HC, Goke R, et al. Reduction of the incretin effect in rats by the glucagon-like peptide 1 receptor antagonist exendin (9-39) amide. Diabetes. 1995;44:16–19
  6. Hansotia T, Baggio LL, Delmeire D, et al. Double incretin receptor knockout (DIRKO) mice reveal an essential role for the enteroinsular axis in transducing the glucoregulatory actions of DPP-IV inhibitors. Diabetes. 2004;53:1326–1335
  7. Miyawaki K, Yamada Y, Yano H, et al. Glucose intolerance caused by a defect in the entero-insular axis: a study in gastric inhibitory polypeptide receptor knockout mice. Proc Natl Acad Sci U S A. 1999;96:14843–14847
  8. Bailey CJ, Flatt PR, Kwasowski P, et al. Immunoreactive gastric inhibitory polypeptide and K cell hyperplasia in obese hyperglycaemic (ob/ob) mice fed high fat and high carbohydrate cafeteria diets. Acta Endocrinol (Copenh). 1986;112:224–229
  9. Roust LR, Stesin M, Go VL, et al. Role of gastric inhibitory polypeptide in postprandial hyperinsulinemia of obesity. Am J Physiol. 1988;254:E767–E774
  10. Kieffer TJ. GIP or not GIP? (That is the question). Trends Pharmacol Sci. 2003;24:110–112
  11. Miyawaki K, Yamada Y, Ban N, et al. Inhibition of gastric inhibitory polypeptide signaling prevents obesity. Nat Med. 2002;8:738–742
  12. McClean PL, Irwin N, Cassidy RS, et al. GIP receptor antagonism reverses obesity, insulin resistance, and associated metabolic disturbances induced in mice by prolonged consumption of high-fat diet. Am J Physiol Endocrinol Metab. 2007;293:E1746–E1755
  13. Kieffer TJ. Glucose-dependent insulinotropic polypeptide. In:  Henry HL,  Norman AW editor. Encyclopedia of hormones. Volume 2:San Diego, CA: Academic Press; 2003;p. 150–157
  14. Fujita Y, Chui JW, King DS, et al. Pax6 and Pdx1 are required for production of glucose-dependent insulinotropic polypeptide (GIP) in proglucagon expressing L-cells. Am J Physiol Endocrinol Metab. 2008;295:E648–E657
  15. Ahren B, Hakanson R, Lundquist I, et al. GIP-like immunoreactivity in glucagon cells (Interactions between GIP and glucagon on insulin release). Acta Physiol Scand. 1981;112:233–242
  16. Smith PH, Merchant FW, Johnson DG, et al. Immunocytochemical localization of a gastric imhibitory polypeptide-like material within A-cells of the endocrine pancreas. Am J Anat. 1977;149:585–590
  17. Alumets J, Hakanson R, O'Dorisio T, et al. Is GIP a glucagon cell constituent?. Histochemistry. 1978;58:253–257
  18. Smith PH. Immunocytochemical localization of glucagonlike and gastric inhibitory polypeptidelike peptides in the pancreatic islets and gastrointestinal tract. Am J Anat. 1983;168:109–118
  19. Sjolund K, Ekelund M, Hakanson R, et al. Gastric inhibitory peptide-like immunoreactivity in glucagon and glicentin cells: properties and origin (An immunocytochemical study using several antisera). J Histochem Cytochem. 1983;31:811–817
  20. Lund PK, Goodman RH, Dee PC, et al. Pancreatic preproglucagon cDNA contains two glucagon-related coding sequences arranged in tandem. Proc Natl Acad Sci U S A. 1982;79:345–349
  21. Lund PK, Goodman RH, Montminy MR, et al. Anglerfish islet pre-proglucagon II (Nucleotide and corresponding amino acid sequence of the cDNA). J Biol Chem. 1983;258:3280–3284
  22. Buchan AM, Ingman-Baker J, Levy J, et al. A comparison of the ability of serum and monoclonal antibodies to gastric inhibitory polypeptide to detect immunoreactive cells in the gastroenteropancreatic system of mammals and reptiles. Histochemistry. 1982;76:341–349
  23. Secor SM, Fehsenfeld D, Diamond J, et al. Responses of python gastrointestinal regulatory peptides to feeding. Proc Natl Acad Sci U S A. 2001;98:13637–13642
  24. Furuta M, Yano H, Zhou A, et al. Defective prohormone processing and altered pancreatic islet morphology in mice lacking active SPC2. Proc Natl Acad Sci U S A. 1997;94:6646–6651
  25. Wideman RD, Yu IL, Webber TD, et al. Improving function and survival of pancreatic islets by endogenous production of glucagon-like peptide 1 (GLP-1). Proc Natl Acad Sci U S A. 2006;103:13468–13473
  26. Morgan LM, Morris BA, Marks V. Radioimmunoassay of gastric inhibitory polypeptide. Ann Clin Biochem. 1978;15:172–177
  27. Pederson RA, Satkunarajah M, McIntosh CH, et al. Enhanced glucose-dependent insulinotropic polypeptide secretion and insulinotropic action in glucagon-like peptide 1 receptor −/− mice. Diabetes. 1998;47:1046–1052
  28. Lewis JT, Dayanandan B, Habener JF, et al. Glucose-dependent insulinotropic polypeptide confers early phase insulin release to oral glucose in rats: demonstration by a receptor antagonist. Endocrinology. 2000;141:3710–3716
  29. Ugleholdt R, Poulsen ML, Holst PJ, et al. Prohormone convertase 1/3 is essential for processing of the glucose-dependent insulinotropic polypeptide precursor. J Biol Chem. 2006;281:11050–11057
  30. Rouille Y, Westermark G, Martin SK, et al. Proglucagon is processed to glucagon by prohormone convertase PC2 in alpha TC1-6 cells. Proc Natl Acad Sci U S A. 1994;91:3242–3246
  31. Wideman RD, Kieffer TJ. Glucose-dependent insulinotropic polypeptide as a regulator of beta cell function and fate. Horm Metab Res. 2004;36:782–786
  32. Pamir N, Lynn FC, Buchan AM, et al. Glucose-dependent insulinotropic polypeptide receptor null mice exhibit compensatory changes in the enteroinsular axis. Am J Physiol Endocrinol Metab. 2003;284:E931–E939
  33. Herbach N, Goeke B, Schneider M, et al. Overexpression of a dominant negative GIP receptor in transgenic mice results in disturbed postnatal pancreatic islet and beta-cell development. Regul Pept. 2005;125:103–117
  34. Portela-Gomes GM, Johansson H, Olding L, et al. Co-localization of neuroendocrine hormones in the human fetal pancreas. Eur J Endocrinol. 1999;141:526–533
  35. Chia CW, Carlson OD, Kim W, et al. Exogenous glucose-dependent insulinotropic polypeptide worsens post prandial hyperglycemia in type 2 diabetes. Diabetes. 2009;58:1342–1349
  36. Usdin TB, Mezey E, Button DC, et al. Gastric inhibitory polypeptide receptor, a member of the secretin-vasoactive intestinal peptide receptor family, is widely distributed in peripheral organs and the brain. Endocrinology. 1993;133:2861–2870
  37. Gremlich S, Porret A, Hani EH, et al. Cloning, functional expression, and chromosomal localization of the human pancreatic islet glucose-dependent insulinotropic polypeptide receptor. Diabetes. 1995;44:1202–1208
  38. Emdin SO, Falkmer S. Phylogeny of insulin (Some evolutionary aspects of insulin production with particular regard to the biosynthesis of insulin in Myxine glutinosa). Acta Paediatr Scand Suppl. 1977;270:15–25
  39. Unger RH, Eisentraut AM, Mc CM, et al. Measurements of endogenous glucagon in plasma and the influence of blood glucose concentration upon its secretion. J Clin Invest. 1962;41:682–689
  40. Amland PF, Jorde R, Revhaug A, et al. Fasting and postprandial GIP values in pigs, rats, dogs, and man measured with five different GIP antisera. Scand J Gastroenterol. 1984;19:1095–1098
  41. Fehmann HC, Goke R, Goke B, et al. Priming effect of glucagon-like peptide-1 (7-36) amide, glucose-dependent insulinotropic polypeptide and cholecystokinin-8 at the isolated perfused rat pancreas. Biochim Biophys Acta. 1991;1091:356–363
  42. Holz GGt, Kuhtreiber WM, Habener JF. Pancreatic beta-cells are rendered glucose-competent by the insulinotropic hormone glucagon-like peptide-1 (7-37). Nature. 1993;361:362–365
  43. Cabrera O, Berman DM, Kenyon NS, et al. The unique cytoarchitecture of human pancreatic islets has implications for islet cell function. Proc Natl Acad Sci U S A. 2006;103:2334–2339
  44. Giordano T, Brigatti C, Podini P, et al. Beta cell chromogranin B is partially segregated in distinct granules and can be released separately from insulin in response to stimulation. Diabetologia. 2008;51:997–1007
  45. Yeung CM, Wong CK, Chung SK, et al. Glucose-dependent insulinotropic polypeptide gene expression in the stomach: revealed by a transgenic mouse study, in situ hybridization and immunohistochemical staining. Mol Cell Endocrinol. 1999;154:161–170
  46. Althage MC, Ford EL, Wang S, et al. Targeted ablation of glucose-dependent insulinotropic polypeptide-producing cells in transgenic mice reduces obesity and insulin resistance induced by a high fat diet. J Biol Chem. 2008;283:18365–18376
  47. Garmendia O, Rodriguez MP, Burrell MA, et al. Immunocytochemical finding of the amidating enzymes in mouse pancreatic A-, B-, and D-cells: a comparison with human and rat. J Histochem Cytochem. 2002;50:1401–1416
  48. Larsson LI, Moody AJ. Glicentin and gastric inhibitory polypeptide immunoreactivity in endocrine cells of the gut and pancreas. J Histochem Cytochem. 1980;28:925–933
  49. Hinke SA, Manhart S, Pamir N, et al. Identification of a bioactive domain in the amino-terminus of glucose-dependent insulinotropic polypeptide (GIP). Biochim Biophys Acta. 2001;1547:143–155
  50. Parthier C, Kleinschmidt M, Neumann P, et al. Crystal structure of the incretin-bound extracellular domain of a G protein-coupled receptor. Proc Natl Acad Sci U S A. 2007;104:13942–13947
  51. Maletti M, Altman JJ, Hoa DH, et al. Evidence of functional gastric inhibitory polypeptide (GIP) receptors in human insulinoma (Binding of synthetic human GIP 1-31 and activation of adenylate cyclase). Diabetes. 1987;36:1336–1340
  52. Irwin DM, Zhang T. Evolution of the vertebrate glucose-dependent insulinotropic polypeptide (GIP) gene. Comp Biochem Physiol. 2006;1:385–395
  53. Wilson ME, Kalamaras JA, German MS. Expression pattern of IAPP and prohormone convertase 1/3 reveals a distinctive set of endocrine cells in the embryonic pancreas. Mech Dev. 2002;115:171–176
  54. Aynsley-Green A. Metabolic and endocrine interrelations in the human fetus and neonate. Am J Clin Nutr. 1985;41:399–417
  55. Pederson RA, Brown JC. Interaction of gastric inhibitory polypeptide, glucose, and arginine on insulin and glucagon secretion from the perfused rat pancreas. Endocrinology. 1978;103:610–615
  56. Meier JJ, Gallwitz B, Siepmann N, et al. Gastric inhibitory polypeptide (GIP) dose-dependently stimulates glucagon secretion in healthy human subjects at euglycaemia. Diabetologia. 2003;46:798–801

 Conflicts of interest The authors disclose no conflicts.

 Funding Timothy Kieffer is a Michael Smith Foundation for Health Research senior scholar and received grant funding from the Juvenile Diabetes Research Foundation and the Michael Smith Foundation for Health Research through the Centre for Human Islet Transplant and Beta-Cell Regeneration; Yukihiro Fujita received scholarship support from the Canadian Diabetes Association and the Stem Cell Network; Rhonda Wideman received scholarship support from the Michael Smith Foundation for Health Research and the Natural Sciences and Engineering Research Council; and Gary Yang received scholarship support from Natural Sciences and Engineering Research Council.

PII: S0016-5085(10)00158-7

doi: 10.1053/j.gastro.2010.01.049

Gastroenterology
Volume 138, Issue 5 , Pages 1966-1975.e1 , May 2010