The Paradoxical Role of Glucose-Dependent Insulinotropic Polypeptide (GIP) in Diet and Eating Behaviour in Health and Disease

  • L. R. Ranganath
  • J. Pinkney


Glucose-dependent insulinotropic polypeptide (GIP) is an intestinal hormone released in response to nutrient intake - mainly carbohydrate and fat. In health it has a number of well-known biological effects, which include stimulation of insulin secretion and maintenance of B-cell mass. However, type 2 diabetes mellitus is characterised by a state of B-cell resistance to GIP. Extrapancreatic receptors for GIP have been demonstrated in a variety of tissues suggesting that it may have important biological effects beyond the pancreas. Of particular interest, GIP peptide/receptor systems may also be present in the brain, suggesting that this peptide may have important biological effects in central pathways. High fat intake leads to hyperplasia of GIP producing intestinal cells, hypersecretion of GIP and the loss of normal inhibitory effect of insulin upon fat-stimulated GIP release, properties that led to it being described as an obesity hormone more than 20 years ago. It is therefore being recognized that GIP receptor blockade may attenuate obesity induced by a high-fat diet. On the other hand GIP agonists also appear to benefit glucose metabolism in obesity and diabetes. The apparent paradox that both pro-GIP and anti-GIP strategies have been shown to be beneficial requires resolution. Since GIP has significant effects on carbohydrate and fat metabolism the GIP pathway may a target for anti-obesity therapies.


Insulin Secretion Cocoa Butter Gastric Inhibitory Polypeptide Hepatic Insulin Extraction Obesity Hormone 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Gastric inhibitory polypeptide or glucose-dependent insulinotropic polypeptide


Glucose-dependent insulinotropic polypeptide receptor


Pancreatic insulin secreting cell


Gastro-intestinal tract


Glucagon-like peptide-1


Type 2 diabetes mellitus


GIP secreting intestinal cell


Dipeptidyl peptidase IV


Monounsaturated fatty acid


Saturated fatty acid


Polyunstaturated fatty acid


Energy expenditure


Pancreatic glucagon secreting cell


Pancreatic somatostatin secreting cell

SGLT 1 transporters

Sodium-dependent glucose transporter 1


GIP receptor gene knockout mice


  1. Aaboe K, Knop FK, Vilsboll T, Volund A, Simonsen U, Deacon CF, et al. J Clin Endocrinol Metab. 2009;94:603–8.PubMedCrossRefGoogle Scholar
  2. Ahrén B, Pettersson M, Uvnäs-Moberg K, Gutniak M, Efendic S. Diabetes Res Clin Pract. 1991;13:153–61.PubMedCrossRefGoogle Scholar
  3. Althage MC, Ford EL, Wang S, Tso P, Polonsky KS, Wice BM. J Biol Chem. 2008;283:18365–76.PubMedCrossRefGoogle Scholar
  4. Beck B, Villaume C, Chayvialle JA, Gariot P, Ulmer M, Desalme A, et al. Peptides. 1984;5:403–6.PubMedCrossRefGoogle Scholar
  5. Boivin M, Flourie B, Rizza RA, Go VL, DiMagno EP. Gastroenterol. 1988;94:387–94.Google Scholar
  6. Brown JC, Dryburgh JR. Can J Biochem. 1971;49:867–72.PubMedGoogle Scholar
  7. Byrne MM, Gliem K, Wank U, Arnold R, Katschinski M, Polonsky KS, et al. Diabetes. 1998;47:1259–65.PubMedCrossRefGoogle Scholar
  8. Cho GJ, Ryu S, Kim YH, Kim YS, Cheon EW, Park JM, et al. Curr Eye Res. 2002;25:381–8.PubMedCrossRefGoogle Scholar
  9. Dalgaard M, Thomsen C, Rasmussen BM, Holst JJ, Hermansen K. Metabol. 2004;53:77–83.CrossRefGoogle Scholar
  10. Daousi C, Wilding JP, Aditya S, Durham BH, Cleator J, Pinkney JH, et al. Clin Endocrinol (Oxf). 2009;71:195–201.CrossRefGoogle Scholar
  11. Deacon CF. Horm Metab Res. 2004;36:761–5.PubMedCrossRefGoogle Scholar
  12. Ding KH, Zhong Q, Xie D, Chen HX, Della-Fera MA, Bollag RJ, et al. Peptides. 2006;27:2750–5.PubMedCrossRefGoogle Scholar
  13. Dogrukol-Ak D, Tore F, Tuncel N. Curr Pharm Des. 2004;10:1325–40.PubMedCrossRefGoogle Scholar
  14. Doupis J, Veves A. Adv Ther. 2008;25:627–43.PubMedCrossRefGoogle Scholar
  15. Ebert R, Creutzfeldt W. Acta Diabetol Lat. 1989;26:1–15.PubMedCrossRefGoogle Scholar
  16. Ebert R, Nauck M, Creutzfeldt W. Horm Metab Res. 1991;23:517–21.PubMedCrossRefGoogle Scholar
  17. Elliott RM, Morgan LM, Tredger JA, Deacon S, Wright J, Marks V. J Endocrinol. 1993;138:159–66.PubMedCrossRefGoogle Scholar
  18. Fehmann HC, Goke R, Goke B. Endocr Rev. 1995;16:390–410.PubMedGoogle Scholar
  19. Flatt PR, Bailey CJ, Kwasowski P, Swanston-Flatt SK. Diabetes Res. 1990;13:23–8.PubMedGoogle Scholar
  20. Flatt PR, Kwasowski P, Howland RJ, Bailey CJ. J Nutr. 1991;121:1123–8.PubMedGoogle Scholar
  21. Gault VA, McClean PL, Cassidy RS, Irwin N, Flatt PR. Diabetol. 2007;50:1752–62.CrossRefGoogle Scholar
  22. Gault VA, Hölscher C. J Neurophysiol. 2008;99:1590–5.PubMedCrossRefGoogle Scholar
  23. Gebhard B, Holst JJ, Biegelmayer C, Miholic J. Dig Dis Sci. 2001;46:1915–23.PubMedCrossRefGoogle Scholar
  24. Green BD, Flatt PR. Best Pract Res Clin Endocrinol Metabol. 2007;21:497–516.CrossRefGoogle Scholar
  25. Gribble FM. Diabet Med. 2008;25:889–94.PubMedCrossRefGoogle Scholar
  26. Hanks JB, Andersen DK, Wise JE, Putnam WS, Meyers WC, Jones RS. Endocrinol. 1984;115:1011–8.CrossRefGoogle Scholar
  27. Hansotia T, Maida A, Flock G, Yamada Y, Tsukiyama K, Seino Y, et al. J Clin Invest. 2007;117:143–52.PubMedCrossRefGoogle Scholar
  28. Higashimoto Y, Opara EC, Liddle RA. Comp Biochem Physiol Part C Pharmacol, Toxicol, Endocrinol. 1995;110:207–14.CrossRefGoogle Scholar
  29. Hsieh J, Hayashi AA, Webb J, Adeli K. Atheroscler Suppl. 2008;9:7–13.PubMedCrossRefGoogle Scholar
  30. Irwin N, Green BD, Gault VA, Cassidy RS, O’Harte FP, Harriott P, et al. Peptides. 2006a;27:893–900.PubMedCrossRefGoogle Scholar
  31. Irwin N, Clarke GC, Green BD, Greer B, Harriott P, Gault VA, et al. Biochem Pharmacol. 2006b;72:719–28.PubMedCrossRefGoogle Scholar
  32. Irwin N, McClean PL, O’Harte FP, Gault VA, Harriott P, Flatt PR. Diabetol. 2007;50:1532–40.CrossRefGoogle Scholar
  33. Irwin N, McClean PL, Patterson S, Hunter K, Flatt PR. Biol Chem. 2009;390:75–80.PubMedCrossRefGoogle Scholar
  34. Isken F, Pfeiffer AF, Nogueiras R, Osterhoff MA, Ristow M, Thorens B, et al. Am J Physiol Endocrinol Metab. 2008;295:E350–5.PubMedCrossRefGoogle Scholar
  35. Jackson KG, Zampelas A, Knapper JM, Roche HM, Gibney MJ, Kafatos A, et al. Am J Clin Nutr. 2000;71:13–20.PubMedGoogle Scholar
  36. Jones PJ, Leitch CA, Pederson RA. Am J Clin Nutr. 1993;57:868–74.PubMedGoogle Scholar
  37. Jorde R, Waldum HL, Burhol PG. Scand J Gastroenterol. 1981;16:219–23.PubMedCrossRefGoogle Scholar
  38. Jones PJ, Namchuk GL, Pederson RA. Metab: Clin & Experim. 1995;44:218–23.CrossRefGoogle Scholar
  39. Kerr BD, Irwin N, Flatt PR, Gault VA. Peptides. 2009;30:219–25.PubMedCrossRefGoogle Scholar
  40. Laferrere B, Teixeira J, McGinty J, Tran H, Egger JR, Colarusso A, et al. J Clin Endocrinol Metab. 2008;93:2479–85.PubMedCrossRefGoogle Scholar
  41. Lardinois CK, Starich GH, Mazzaferri EL, DeLett A. J Am Coll Nutr. 1987;6:507–15.PubMedGoogle Scholar
  42. Lardinois CK, Starich GH, Mazzaferri EL. J Am Coll Nutr. 1988;7:241–7.PubMedCrossRefGoogle Scholar
  43. Li L, Wice BM. Am J Physiology – Endocrinol & Metab. 2005;288:E208–15.CrossRefGoogle Scholar
  44. Marks V. Current Approaches Obesity, Eds James WPT & Parker SW, Duphar Medical Relations, 1988, pp 13–20.PubMedCrossRefGoogle Scholar
  45. Mazzaferri EL, Starich GH, St Jeor ST. J Clin Endocrinol Metab. 1984;58:640–5.PubMedCrossRefGoogle Scholar
  46. McIntyre N, Holdsworth CD, Turner DS. Lancet. 1964;2:20–1.PubMedCrossRefGoogle Scholar
  47. McIntosh CH, Widenmaier S, Kim SJ. Vitam Horm. 2009;80:409–71.PubMedCrossRefGoogle Scholar
  48. Meier JJ, Nauck MA, Schmidt WE, Gallwitz B. Regul Pept. 2002;107:1–13.PubMedCrossRefGoogle Scholar
  49. Meier JJ, Gallwitz B, Siepmann N, Holst JJ, Deacon CF, Schmidt WE, et al. Diabetolog. 2003;46:798–801.CrossRefGoogle Scholar
  50. Miyawaki K, Yamada Y, Ban N, Ihara Y, Tsukiyama K, Zhou H, et al. Nat Med. 2002;8:738–42.PubMedCrossRefGoogle Scholar
  51. Miyawaki K, Yamada Y, Yano H, Niwa H, Ban N, Ihara Y, et al. Proc Nat Acad Sci USA. 1999;96:14843–7.PubMedCrossRefGoogle Scholar
  52. Musso G, Gambino R, Pacini G, De Michieli F, Cassader M. Am J Clin Nutr. 2009;89:558–67.PubMedCrossRefGoogle Scholar
  53. Naitoh R, Miyawaki K, Harada N, Mizunoya W, Toyoda K, Fushiki T, et al. Biochem Biophys Res Comm. 2008;376:21–5.PubMedCrossRefGoogle Scholar
  54. Nakajima T, Nakajima E, Fukiage C, Azuma M, Shearer TR. Exp Eye Res. 2002;74:231–6.PubMedCrossRefGoogle Scholar
  55. Nauck M, Stockmann F, Ebert R, Creutzfeldt W. Diabetologia. 1986;29:46–52.PubMedCrossRefGoogle Scholar
  56. Nunes C, Malmlof K. Br J Nutr. 1992;68:693–700.PubMedCrossRefGoogle Scholar
  57. Nyberg J, Anderson MF, Meister B, Alborn AM, Strom AK, Brederlau A, et al. J Neurosci Res. 2005;25:1816–25.Google Scholar
  58. Nyberg J, Jacobsson C, Anderson MF, Eriksson PS. J Neurosci Res. 2007;85:2099–119.PubMedCrossRefGoogle Scholar
  59. O’Donovan DG, Doran S, Feinle-Bisset C, Jones KL, Meyer JH, Wishart JM, et al. J Clin Endocrinol Metab. 2004;89:3431–5.PubMedCrossRefGoogle Scholar
  60. O’Harte FP, Mooney MH, Kelly CM, Flatt PR. J Endocrinol. 2000;165:639–48.PubMedCrossRefGoogle Scholar
  61. Patriti A, Facchiano E, Sanna A, Gullà N, Donini A. Obes Surg. 2004;14:840–8. 121.PubMedCrossRefGoogle Scholar
  62. Pederson RA, Satkunarajah M, McIntosh CH, Scrocchi LA, Flamez D, Schuit F, et al. Diabetes. 1998;47:1046–52.PubMedCrossRefGoogle Scholar
  63. Peracchi M, Santangelo A, Conte D, et al. Br J Nutr. 2000;83:623–8.PubMedCrossRefGoogle Scholar
  64. Ranganath L, Norris F, Morgan L, Wright J, Marks V. Diabetes Med. 1998;15:120–4.CrossRefGoogle Scholar
  65. Ranganath L, Schaper F, Gama R, Morgan L, Wright J, Teale D, et al. Diabetes Metab Res Rev. 1999;15:390–4.PubMedCrossRefGoogle Scholar
  66. Ranganath LR, Beety JM, Wright J, Morgan LM. Horm Metab Res. 2001;33:57–61.PubMedCrossRefGoogle Scholar
  67. Rudovich NN, Rochlitz HJ, Pfeiffer AF. Diabetes. 2004;53:2359–65.PubMedCrossRefGoogle Scholar
  68. Shak JR, Roper J, Perez-Perez GI, Tseng CH, Francois F, Gamagaris Z, et al. Obes Surg. 2008;18:1089–96.PubMedCrossRefGoogle Scholar
  69. Shimotoyodome A, Fukuoka D, Suzuki J, Fujii Y, Mizuno T, Meguro S, Tokimitsu I, Hase T. Endocrinol 2009 Jan 29 [Epub].PubMedCrossRefGoogle Scholar
  70. Shuster LT, Go VL, Rizza RA, O’Brien PC, Service FJ. Diabetes. 1988;37:200–3.PubMedCrossRefGoogle Scholar
  71. Singh SK, Bartoo AC, Krishnan S, MO Schwartz JH, Michael Wolfe M. Obesity (Silver Spring). 2008;16:2412–6.CrossRefGoogle Scholar
  72. Takahashi M, Sasaki I, Naito H, Funayama Y, Shibata C, Matsuno S. Tohoku J Exp Med. 1996;178:151–62.PubMedCrossRefGoogle Scholar
  73. Thomsen C, Rasmussen O, Lousen T, Holst JJ, Fenselau S, Schrezenmeir J, et al. Am J Clin Nutr. 1999;69:1135–43.PubMedGoogle Scholar
  74. Tsiolakis D, Marks V. Horm Metab Res. 1984;16:226–9.PubMedCrossRefGoogle Scholar
  75. Wideman RD, Kieffer TJ. Horm Metab Res. 2004;36:782–6.PubMedCrossRefGoogle Scholar
  76. Wolfe MM, Zhao KB, Glazier KD, Jarboe LA, Tseng CC. Am J Physiol Gastrointest Liver Physiol. 2000;279:G561–6.PubMedGoogle Scholar
  77. Yamada C, Yamada Y, Tsukiyama K, Yamada K, Yamane S, Harada N, et al. Biochem Biophys Res Commun. 2007;364:175–80.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of Clinical ChemistryRoyal Liverpool University HospitalLiverpoolUK

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