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The Role of Incretins in Insulin Secretion

  • Marzieh SalehiEmail author
Reference work entry

Abstract

The notion that gut factors produced in response to nutrient ingestion are capable of stimulating the endocrine pancreas and consequently reducing glycemic levels was introduced more than 100 years ago. These gut factors were subsequently called incretins, and the augmented insulin response to nutrient given orally compared to nutrient administered intravenously was named “incretin effect.” This chapter focuses on the mechanisms of the synthesis and actions of the incretin peptides, glucagon-like peptide 1, and glucose-dependent insulinotropic polypeptide. In addition, alteration in incretin axis in type 2 diabetes and therapeutic relevance of these peptides will be highlighted. Finally, the role of incretin axis in diabetes remission after gastrointestinal surgeries for treatment of obesity will be briefly discussed.

Keywords

Insulin secretion Incretin effect GLP-1 GIP type 2 diabetes bariatric surgery 

References

  1. 1.
    Horowitz M, Edelbroek MA, Wishart JM, Straathof JW. Relationship between oral glucose tolerance and gastric emptying in normal healthy subjects. Diabetologia. 1993;36(9):857–62.PubMedCrossRefGoogle Scholar
  2. 2.
    Tillil H, Shapiro ET, Miller MA, Karrison T, Frank BH, Galloway JA, et al. Dose-dependent effects of oral and intravenous glucose on insulin secretion and clearance in normal humans. Am J Physiol. 1988;254(3 Pt 1):E349–57.PubMedGoogle Scholar
  3. 3.
    Avignon A, Radauceanu A, Monnier L. Nonfasting plasma glucose is a better marker of diabetic control than fasting plasma glucose in type 2 diabetes. Diabetes Care. 1997;20(12):1822–6.PubMedCrossRefGoogle Scholar
  4. 4.
    Moore B, Edie E, Abram J. On the treatment of diabetes mellitus by acid extract of duodenal mucous membrane. Biochem J. 1906;1:28–38.PubMedPubMedCentralCrossRefGoogle Scholar
  5. 5.
    McIntyre N, Holdsworth CD, Turner DS. New interpretation of oral glucose tolerance. Lancet. 1964;41:20–1.CrossRefGoogle Scholar
  6. 6.
    Zunz E, La Barre J. Contributions a letude des variations physiologiques de la secretion interne du pancreas: relations entere les secretions externe et intene du pancreas. Arch Int Physiol Biochim. 1929;31:20–44.Google Scholar
  7. 7.
    Nauck MA, Homberger E, Siegel EG, Allen RC, Eaton RP, Ebert R, et al. Incretin effects of increasing glucose loads in man calculated from venous insulin and C-peptide responses. J Clin Endocrinol Metab. 1986;63(2):492–8.PubMedCrossRefGoogle Scholar
  8. 8.
    Vilsboll T, Krarup T, Madsbad S, Holst JJ. Both GLP-1 and GIP are insulinotropic at basal and postprandial glucose levels and contribute nearly equally to the incretin effect of a meal in healthy subjects. Regul Pept. 2003;114(2–3):115–21.PubMedCrossRefGoogle Scholar
  9. 9.
    Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology. 2007;132(6):2131–57.PubMedCrossRefGoogle Scholar
  10. 10.
    Creutzfeldt W, Ebert R. New developments in the incretin concept. Diabetologia. 1985;28(8):565–73.PubMedCrossRefGoogle Scholar
  11. 11.
    Teff KL, Townsend RR. Early phase insulin infusion and muscarinic blockade in obese and lean subjects. Am J Physiol. 1999;277(1 Pt 2):R198–208.PubMedGoogle Scholar
  12. 12.
    Teff KL, Levin BE, Engelman K. Oral sensory stimulation in men: effects on insulin, C-peptide, and catecholamines. Am J Physiol. 1993;265(6 Pt 2):R1223–30.PubMedGoogle Scholar
  13. 13.
    D’Alessio DA, Kieffer TJ, Taborsky Jr GJ, Havel PJ. Activation of the parasympathetic nervous system is necessary for normal meal-induced insulin secretion in rhesus macaques. J Clin Endocrinol Metab. 2001;86(3):1253–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Ahren B, Holst JJ. The cephalic insulin response to meal ingestion in humans is dependent on both cholinergic and noncholinergic mechanisms and is important for postprandial glycemia. Diabetes. 2001;50(5):1030–8.PubMedCrossRefGoogle Scholar
  15. 15.
    Eissele R, Goke R, Willemer S, Harthus HP, Vermeer H, Arnold R, et al. Glucagon-like peptide-1 cells in the gastrointestinal tract and pancreas of rat, pig and man. Eur J Clin Invest. 1992;22(4):283–91.PubMedCrossRefGoogle Scholar
  16. 16.
    Layer P, Holst JJ, Grandt D, Goebell H. Ileal release of glucagon-like peptide-1 (GLP-1). Association with inhibition of gastric acid secretion in humans. Dig Dis Sci. 1995;40(5):1074–82.PubMedCrossRefGoogle Scholar
  17. 17.
    Schirra J, Katschinski M, Weidmann C, Schafer T, Wank U, Arnold R, et al. Gastric emptying and release of incretin hormones after glucose ingestion in humans. J Clin Invest. 1996;97(1):92–103.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Alsalim W, Omar B, Pacini G, Bizzotto R, Mari A, Ahren B. Incretin and islet hormone responses to meals of increasing size in healthy subjects. J Clin Endocrinol Metab. 2015;100(2):561–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Rocca AS, Brubaker PL. Role of the vagus nerve in mediating proximal nutrient-induced glucagon-like peptide-1 secretion. Endocrinology. 1999;140(4):1687–94.PubMedCrossRefGoogle Scholar
  20. 20.
    Alsalim W, Tura A, Pacini G, Omar B, Bizzotto R, Mari A, et al. Mixed meal ingestion diminishes glucose excursion in comparison with glucose ingestion via several adaptive mechanisms in people with and without type 2 diabetes. Diabetes Obes Metab. 2016;18(1):24-33.Google Scholar
  21. 21.
    Deacon CF, Johnsen AH, Holst JJ. Degradation of glucagon-like peptide-1 by human plasma in vitro yields an N-terminally truncated peptide that is a major endogenous metabolite in vivo. J Clin Endocrinol Metab. 1995;80(3):952–7.PubMedGoogle Scholar
  22. 22.
    Vahl TP, Paty BW, Fuller BD, Prigeon RL, D’Alessio DA. Effects of GLP-1-(7-36)NH2, GLP-1-(7-37), and GLP-1- (9-36)NH2 on intravenous glucose tolerance and glucose-induced insulin secretion in healthy humans. J Clin Endocrinol Metab. 2003;88(4):1772–9.PubMedCrossRefGoogle Scholar
  23. 23.
    Salehi M, Aulinger BA, D’Alessio DA. Targeting beta-cell mass in type 2 diabetes: promise and limitations of new drugs based on incretins. Endocr Rev. 2008;29(3):367–79.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Wang Y, Perfetti R, Greig NH, Holloway HW, DeOre KA, Montrose-Rafizadeh C, et al. Glucagon-like peptide-1 can reverse the age-related decline in glucose tolerance in rats. J Clin Invest. 1997;99(12):2883–9.PubMedPubMedCentralCrossRefGoogle Scholar
  25. 25.
    Scrocchi LA, Brown TJ, MaClusky N, Brubaker PL, Auerbach AB, Joyner AL, et al. Glucose intolerance but normal satiety in mice with a null mutation in the glucagon-like peptide 1 receptor gene. Nat Med. 1996;2(11):1254–8.PubMedCrossRefGoogle Scholar
  26. 26.
    Li Y, Hansotia T, Yusta B, Ris F, Halban PA, Drucker DJ. Glucagon-like peptide-1 receptor signaling modulates beta cell apoptosis. J Biol Chem. 2003;278(1):471–8.PubMedCrossRefGoogle Scholar
  27. 27.
    De Leon DD, Deng S, Madani R, Ahima RS, Drucker DJ, Stoffers DA. Role of endogenous glucagon-like peptide-1 in islet regeneration after partial pancreatectomy. Diabetes. 2003;52(2):365–71.PubMedCrossRefGoogle Scholar
  28. 28.
    Xu G, Stoffers DA, Habener JF, Bonner-Weir S. Exendin-4 stimulates both beta-cell replication and neogenesis, resulting in increased beta-cell mass and improved glucose tolerance in diabetic rats. Diabetes. 1999;48(12):2270–6.PubMedCrossRefGoogle Scholar
  29. 29.
    Bulotta A, Hui H, Anastasi E, Bertolotto C, Boros LG, Di Mario U, et al. Cultured pancreatic ductal cells undergo cell cycle re-distribution and beta-cell-like differentiation in response to glucagon-like peptide-1. J Mol Endocrinol. 2002;29(3):347–60.PubMedCrossRefGoogle Scholar
  30. 30.
    Wang Q, Brubaker PL. Glucagon-like peptide-1 treatment delays the onset of diabetes in 8 week-old db/db mice. Diabetologia. 2002;45(9):1263–73.PubMedCrossRefGoogle Scholar
  31. 31.
    Schirra J, Nicolaus M, Roggel R, Katschinski M, Storr M, Woerle HJ, et al. Endogenous glucagon-like peptide 1 controls endocrine pancreatic secretion and antro-pyloro-duodenal motility in humans. Gut. 2006;55(2):243–51.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Naslund E, Gutniak M, Skogar S, Rossner S, Hellstrom PM. Glucagon-like peptide 1 increases the period of postprandial satiety and slows gastric emptying in obese men. Am J Clin Nutr. 1998;68(3):525–30.PubMedGoogle Scholar
  33. 33.
    Imeryuz N, Yegen BC, Bozkurt A, Coskun T, Villanueva-Penacarrillo ML, Ulusoy NB. Glucagon-like peptide-1 inhibits gastric emptying via vagal afferent-mediated central mechanisms. Am J Physiol. 1997;273(4 Pt 1):G920–7.PubMedGoogle Scholar
  34. 34.
    Salehi M, Vahl TP, D’Alessio DA. Regulation of islet hormone release and gastric emptying by endogenous glucagon-like peptide 1 after glucose ingestion. J Clin Endocrinol Metab. 2008;93(12):4909–16.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Nicolaus M, Brodl J, Linke R, Woerle HJ, Goke B, Schirra J. Endogenous GLP-1 regulates postprandial glycemia in humans: relative contributions of insulin, glucagon, and gastric emptying. J Clin Endocrinol Metab. 2011;96(1):229–36.PubMedCrossRefGoogle Scholar
  36. 36.
    Salehi M, Aulinger B, Prigeon RL, D’Alessio DA. Effect of endogenous GLP-1 on insulin secretion in type 2 diabetes. Diabetes. 2010;59(6):1330–7.PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Reimann F. Molecular mechanisms underlying nutrient detection by incretin-secreting cells. Int Dairy J. 2010;20(4):236–42.PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Tseng CC, Kieffer TJ, Jarboe LA, Usdin TB, Wolfe MM. Postprandial stimulation of insulin release by glucose-dependent insulinotropic polypeptide (GIP). Effect of a specific glucose-dependent insulinotropic polypeptide receptor antagonist in the rat. J Clin Invest. 1996;98(11):2440–5.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Irwin N, Gault VA, Green BD, Greer B, McCluskey JT, Harriott P, et al. Effects of short-term chemical ablation of the GIP receptor on insulin secretion, islet morphology and glucose homeostasis in mice. Biol Chem. 2004;385(9):845–52.PubMedCrossRefGoogle Scholar
  40. 40.
    Miyawaki K, Yamada Y, Yano H, Niwa H, Ban N, Ihara Y, 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(26):14843–7.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Miyawaki K, Yamada Y, Ban N, Ihara Y, Tsukiyama K, Zhou H, et al. Inhibition of gastric inhibitory polypeptide signaling prevents obesity. Nat Med. 2002;8(7):738–42.PubMedCrossRefGoogle Scholar
  42. 42.
    Gault VA, McClean PL, Cassidy RS, Irwin N, Flatt PR. Chemical gastric inhibitory polypeptide receptor antagonism protects against obesity, insulin resistance, glucose intolerance and associated disturbances in mice fed high-fat and cafeteria diets. Diabetologia. 2007;50(8):1752–62.PubMedCrossRefGoogle Scholar
  43. 43.
    Althage MC, Ford EL, Wang S, Tso P, Polonsky KS, Wice BM. 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(26):18365–76.PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Ehses JA, Casilla VR, Doty T, Pospisilik JA, Winter KD, Demuth HU, et al. Glucose-dependent insulinotropic polypeptide promotes beta-(INS-1) cell survival via cyclic adenosine monophosphate-mediated caspase-3 inhibition and regulation of p38 mitogen-activated protein kinase. Endocrinology. 2003;144(10):4433–45.PubMedCrossRefGoogle Scholar
  45. 45.
    Vilsboll T, Krarup T, Madsbad S, Holst JJ. Defective amplification of the late phase insulin response to glucose by GIP in obese Type II diabetic patients. Diabetologia. 2002;45(8):1111–9.PubMedCrossRefGoogle Scholar
  46. 46.
    Lund A, Vilsboll T, Bagger JI, Holst JJ, Knop FK. The separate and combined impact of the intestinal hormones, GIP, GLP-1, and GLP-2, on glucagon secretion in type 2 diabetes. Am J Physiol Endocrinol Metab. 2011;300(6):E1038–46.PubMedCrossRefGoogle Scholar
  47. 47.
    Andersen DK, Elahi D, Brown JC, Tobin JD, Andres R. Oral glucose augmentation of insulin secretion. Interactions of gastric inhibitory polypeptide with ambient glucose and insulin levels. J Clin Invest. 1978;62(1):152–61.PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Nauck MA, Heimesaat MM, Behle K, Holst JJ, Nauck MS, Ritzel R, et al. Effects of glucagon-like peptide 1 on counterregulatory hormone responses, cognitive functions, and insulin secretion during hyperinsulinemic, stepped hypoglycemic clamp experiments in healthy volunteers. J Clin Endocrinol Metab. 2002;87(3):1239–46.PubMedCrossRefGoogle Scholar
  49. 49.
    Qualmann C, Nauck MA, Holst JJ, Orskov C, Creutzfeldt W. Insulinotropic actions of intravenous glucagon-like peptide-1 (GLP-1) [7-36 amide] in the fasting state in healthy subjects. Acta Diabetol. 1995;32(1):13–6.PubMedCrossRefGoogle Scholar
  50. 50.
    Pamir N, Lynn FC, Buchan AM, Ehses J, Hinke SA, Pospisilik JA, et al. Glucose-dependent insulinotropic polypeptide receptor null mice exhibit compensatory changes in the enteroinsular axis. Am J Physiol Endocrinol Metab. 2003;284(5):E931–9.PubMedCrossRefGoogle Scholar
  51. 51.
    Pederson RA, Satkunarajah M, McIntosh CH, Scrocchi LA, Flamez D, Schuit F, et al. Enhanced glucose-dependent insulinotropic polypeptide secretion and insulinotropic action in glucagon-like peptide 1 receptor −/− mice. Diabetes. 1998;47(7):1046–52.PubMedCrossRefGoogle Scholar
  52. 52.
    Hansen L, Lampert S, Mineo H, Holst JJ. Neural regulation of glucagon-like peptide-1 secretion in pigs. Am J Physiol Endocrinol Metab. 2004;287(5):E939–47.PubMedCrossRefGoogle Scholar
  53. 53.
    Burcelin R, Da Costa A, Drucker D, Thorens B. Glucose competence of the hepatoportal vein sensor requires the presence of an activated glucagon-like peptide-1 receptor. Diabetes. 2001;50(8):1720–8.PubMedCrossRefGoogle Scholar
  54. 54.
    Vahl TP, Tauchi M, Durler TS, Elfers EE, Fernandes TM, Bitner RD, et al. Glucagon-like peptide-1 (GLP-1) receptors expressed on nerve terminals in the portal vein mediate the effects of endogenous GLP-1 on glucose tolerance in rats. Endocrinology. 2007;148(10):4965–73.Google Scholar
  55. 55.
    Nauck MA, Niedereichholz U, Ettler R, Holst JJ, Orskov C, Ritzel R, et al. Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans. Am J Physiol. 1997;273(5 Pt 1):E981–8.PubMedGoogle Scholar
  56. 56.
    Wettergren A, Schjoldager B, Mortensen PE, Myhre J, Christiansen J, Holst JJ. Truncated GLP-1 (proglucagon 78-107-amide) inhibits gastric and pancreatic functions in man. Dig Dis Sci. 1993;38(4):665–73.PubMedCrossRefGoogle Scholar
  57. 57.
    Flint A, Raben A, Astrup A, Holst JJ. Glucagon-like peptide 1 promotes satiety and suppresses energy intake in humans. J Clin Invest. 1998;101(3):515–20.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Prigeon RL, Quddusi S, Paty B, D’Alessio DA. Suppression of glucose production by GLP-1 independent of islet hormones: a novel extrapancreatic effect. Am J Physiol Endocrinol Metab. 2003;285(4):E701–7.PubMedCrossRefGoogle Scholar
  59. 59.
    Mabilleau G. Incretins and bone: friend or foe? Curr Opin Pharmacol. 2015;22:72–8.PubMedCrossRefGoogle Scholar
  60. 60.
    Nauck M, Stockmann F, Ebert R, Creutzfeldt W. Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia. 1986;29(1):46–52.PubMedCrossRefGoogle Scholar
  61. 61.
    Perley MJ, Kipnis DM. Plasma insulin responses to oral and intravenous glucose: studies in normal and diabetic subjects. J Clin Invest. 1967;46(12):1954–62.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Mari A, Bagger JI, Ferrannini E, Holst JJ, Knop FK, Vilsboll T. Mechanisms of the incretin effect in subjects with normal glucose tolerance and patients with type 2 diabetes. PLoS One. 2013;8(9):e73154.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Muscelli E, Mari A, Natali A, Astiarraga BD, Camastra S, Frascerra S, et al. Impact of incretin hormones on beta-cell function in subjects with normal or impaired glucose tolerance. Am J Physiol Endocrinol Metab. 2006;291(6):E1144–50.PubMedCrossRefGoogle Scholar
  64. 64.
    Nielsen ST, Janum S, Krogh-Madsen R, Solomon TP, Moller K. The incretin effect in critically ill patients: a case-control study. Crit Care. 2015;19(1):402.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Henchoz E, D’Alessio DA, Gillet M, Halkic N, Matzinger O, Goy JJ, et al. Impaired insulin response after oral but not intravenous glucose in heart- and liver-transplant recipients. Transplantation. 2003;76(6):923–9.PubMedCrossRefGoogle Scholar
  66. 66.
    Michaliszyn SF, Mari A, Lee S, Bacha F, Tfayli H, Farchoukh L, et al. beta-cell function, incretin effect, and incretin hormones in obese youth along the span of glucose tolerance from normal to prediabetes to type 2 diabetes. Diabetes. 2014;63(11):3846–55.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Orskov C, Jeppesen J, Madsbad S, Holst JJ. Proglucagon products in plasma of noninsulin-dependent diabetics and nondiabetic controls in the fasting state and after oral glucose and intravenous arginine. J Clin Invest. 1991;87(2):415–23.PubMedPubMedCentralCrossRefGoogle Scholar
  68. 68.
    Fukase N, Manaka H, Sugiyama K, Takahashi H, Igarashi M, Daimon M, et al. Response of truncated glucagon-like peptide-1 and gastric inhibitory polypeptide to glucose ingestion in non-insulin dependent diabetes mellitus. Effect of sulfonylurea therapy. Acta Diabetol. 1995;32(3):165–9.PubMedCrossRefGoogle Scholar
  69. 69.
    Vaag AA, Holst JJ, Volund A, Beck-Nielsen HB. Gut incretin hormones in identical twins discordant for non-insulin-dependent diabetes mellitus (NIDDM)–evidence for decreased glucagon-like peptide 1 secretion during oral glucose ingestion in NIDDM twins. Eur J Endocrinol. 1996;135(4):425–32.PubMedCrossRefGoogle Scholar
  70. 70.
    Vollmer K, Holst JJ, Baller B, Ellrichmann M, Nauck MA, Schmidt WE, et al. Predictors of incretin concentrations in subjects with normal, impaired, and diabetic glucose tolerance. Diabetes. 2008;57(3):678–87.PubMedCrossRefGoogle Scholar
  71. 71.
    Krarup T. Immunoreactive gastric inhibitory polypeptide. Endocr Rev. 1988;9(1):122–34.PubMedCrossRefGoogle Scholar
  72. 72.
    Ebert R, Creutzfeldt W. Gastrointestinal peptides and insulin secretion. Diabetes Metab Rev. 1987;3(1):1–26.PubMedCrossRefGoogle Scholar
  73. 73.
    Kjems LL, Holst JJ, Volund A, Madsbad S. The influence of GLP-1 on glucose-stimulated insulin secretion: effects on beta-cell sensitivity in type 2 and nondiabetic subjects. Diabetes. 2003;52(2):380–6.PubMedCrossRefGoogle Scholar
  74. 74.
    Hojberg PV, Vilsboll T, Rabol R, Knop FK, Bache M, Krarup T, et al. Four weeks of near-normalisation of blood glucose improves the insulin response to glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide in patients with type 2 diabetes. Diabetologia. 2009;52(2):199–207.PubMedCrossRefGoogle Scholar
  75. 75.
    Ahren B, Larsson H, Holst JJ. Effects of glucagon-like peptide-1 on islet function and insulin sensitivity in noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab. 1997;82(2):473–8.PubMedGoogle Scholar
  76. 76.
    Elahi D, McAloon-Dyke M, Fukagawa NK, Meneilly GS, Sclater AL, Minaker KL, et al. The insulinotropic actions of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (7-37) in normal and diabetic subjects. Regul Pept. 1994;51(1):63–74.PubMedCrossRefGoogle Scholar
  77. 77.
    Nauck MA, Heimesaat MM, Orskov C, Holst JJ, Ebert R, Creutzfeldt W. Preserved incretin activity of glucagon-like peptide 1 [7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus. J Clin Invest. 1993;91(1):301–7.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Nauck MA, Kleine N, Orskov C, Holst JJ, Willms B, Creutzfeldt W. Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7-36 amide) in type 2 (non-insulin-dependent) diabetic patients. Diabetologia. 1993;36(8):741–4.PubMedCrossRefGoogle Scholar
  79. 79.
    Rachman J, Gribble FM, Barrow BA, Levy JC, Buchanan KD, Turner RC. Normalization of insulin responses to glucose by overnight infusion of glucagon-like peptide 1 (7-36) amide in patients with NIDDM. Diabetes. 1996;45(11):1524–30.PubMedCrossRefGoogle Scholar
  80. 80.
    Quddusi S, Vahl TP, Hanson K, Prigeon RL, D’Alessio DA. Differential effects of acute and extended infusions of glucagon-like peptide-1 on first- and second-phase insulin secretion in diabetic and nondiabetic humans. Diabetes Care. 2003;26(3):791–8.PubMedCrossRefGoogle Scholar
  81. 81.
    Rachman J, Barrow BA, Levy JC, Turner RC. Near-normalisation of diurnal glucose concentrations by continuous administration of glucagon-like peptide-1 (GLP-1) in subjects with NIDDM. Diabetologia. 1997;40(2):205–11.PubMedCrossRefGoogle Scholar
  82. 82.
    Krarup T, Saurbrey N, Moody AJ, Kuhl C, Madsbad S. Effect of porcine gastric inhibitory polypeptide on beta-cell function in type I and type II diabetes mellitus. Metabolism. 1987;36(7):677–82.PubMedCrossRefGoogle Scholar
  83. 83.
    Schauer PR, Ikramuddin S, Gourash W, Ramanathan R, Luketich J. Outcomes after laparoscopic Roux-en-Y gastric bypass for morbid obesity. Ann Surg. 2000;232(4):515–29.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Peterli R, Wolnerhanssen B, Peters T, Devaux N, Kern B, Christoffel-Courtin C, et al. Improvement in glucose metabolism after bariatric surgery: comparison of laparoscopic Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy: a prospective randomized trial. Ann Surg. 2009;250(2):234–41.PubMedCrossRefGoogle Scholar
  85. 85.
    Jorgensen NB, Jacobsen SH, Dirksen C, Bojsen-Moller KN, Naver L, Hvolris L, et al. Acute and long-term effects of Roux-en-Y gastric bypass on glucose metabolism in subjects with Type 2 diabetes and normal glucose tolerance. Am J Physiol Endocrinol Metab. 2012;303(1):E122–31.PubMedCrossRefGoogle Scholar
  86. 86.
    Salehi M, Gastaldelli A, D’Alessio DA. Blockade of glucagon-like peptide 1 receptor corrects postprandial hypoglycemia after gastric bypass. Gastroenterology. 2014;146(3):669–80 e2.PubMedCrossRefGoogle Scholar
  87. 87.
    Salehi M, Gastaldelli A, D’Alessio DA. Altered islet function and insulin clearance cause hyperinsulinemia in gastric bypass patients with symptoms of postprandial hypoglycemia. J Clin Endocrinol Metab. 2014;99(6):2008–17.Google Scholar
  88. 88.
    Laferrere B, Heshka S, Wang K, Khan Y, McGinty J, Teixeira J, et al. Incretin levels and effect are markedly enhanced 1 month after Roux-en-Y gastric bypass surgery in obese patients with type 2 diabetes. Diabetes Care. 2007;30(7):1709–16.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Laferrere B, Teixeira J, McGinty J, Tran H, Egger JR, Colarusso A, et al. Effect of weight loss by gastric bypass surgery versus hypocaloric diet on glucose and incretin levels in patients with type 2 diabetes. J Clin Endocrinol Metab. 2008;93(7):2479–85.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Korner J, Bessler M, Inabnet W, Taveras C, Holst JJ. Exaggerated glucagon-like peptide-1 and blunted glucose-dependent insulinotropic peptide secretion are associated with Roux-en-Y gastric bypass but not adjustable gastric banding. Surg Obes Relat Dis. 2007;3(6):597–601.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Peterli R, Steinert RE, Woelnerhanssen B, Peters T, Christoffel-Courtin C, Gass M, et al. Metabolic and hormonal changes after laparoscopic Roux-en-Y gastric bypass and sleeve gastrectomy: a randomized, prospective trial. Obes Surg. 2012;22(5):740–8.PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Salehi M, D’Alessio DA. Effects of glucagon like peptide-1 to mediate glycemic effects of weight loss surgery. Rev Endocr Metab Disord. 2014;15(3):171–9.PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Nguyen NQ, Debreceni TL, Bambrick JE, Bellon M, Wishart J, Standfield S, et al. Rapid gastric and intestinal transit is a major determinant of changes in blood glucose, intestinal hormones, glucose absorption and postprandial symptoms after gastric bypass. Obesity (Silver Spring). 2014;22(9):2003–9.Google Scholar
  94. 94.
    Camastra S, Muscelli E, Gastaldelli A, Holst JJ, Astiarraga B, Baldi S, et al. Long-term effects of bariatric surgery on meal disposal and beta-cell function in diabetic and nondiabetic patients. Diabetes. 2013;62(11):3709–17.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Jacobsen SH, Bojsen-Moller KN, Dirksen C, Jorgensen NB, Clausen TR, Wulff BS, et al. Effects of gastric bypass surgery on glucose absorption and metabolism during a mixed meal in glucose-tolerant individuals. Diabetologia. 2013;56(10):2250–4.PubMedCrossRefGoogle Scholar
  96. 96.
    Chaikomin R, Doran S, Jones KL, Feinle-Bisset C, O’Donovan D, Rayner CK, et al. Initially more rapid small intestinal glucose delivery increases plasma insulin, GIP, and GLP-1 but does not improve overall glycemia in healthy subjects. Am J Physiol Endocrinol Metab. 2005;289(3):E504–7.PubMedCrossRefGoogle Scholar
  97. 97.
    Salehi M, Prigeon RL, D’Alessio DA. Gastric bypass surgery enhances glucagon-like peptide 1-stimulated postprandial insulin secretion in humans. Diabetes. 2011;60(9):2308–14.PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    Dutia R, Brakoniecki K, Bunker P, Paultre F, Homel P, Carpentier AC, et al. Limited recovery of beta-cell function after gastric bypass despite clinical diabetes remission. Diabetes. 2014;63(4):1214–23.PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Salehi M, Gastaldelli A, D’Alessio DA. Evidence from a single individual that increased plasma GLP-1 and GLP-1-stimulated insulin secretion after gastric bypass are independent of foregut exclusion. Diabetologia. 2014;57(7):1495–9.PubMedPubMedCentralCrossRefGoogle Scholar
  100. 100.
    Jorgensen NB, Dirksen C, Bojsen-Moller KN, Jacobsen SH, Worm D, Hansen DL, et al. Exaggerated glucagon-like peptide 1 response is important for improved beta-cell function and glucose tolerance after Roux-en-Y gastric bypass in patients with type 2 diabetes. Diabetes. 2013;62(9):3044–52.PubMedPubMedCentralCrossRefGoogle Scholar
  101. 101.
    Shah M, Law JH, Micheletto F, Sathananthan M, Dalla Man C, Cobelli C, et al. Contribution of endogenous glucagon-like peptide 1 to glucose metabolism after Roux-en-Y gastric bypass. Diabetes. 2014;63(2):483–93.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Lee WJ, Chong K, Ser KH, Lee YC, Chen SC, Chen JC, et al. Gastric bypass vs sleeve gastrectomy for type 2 diabetes mellitus: a randomized controlled trial. Arch Surg. 2011;146(2):143–8.PubMedCrossRefGoogle Scholar
  103. 103.
    Cohen RV, Pinheiro JC, Schiavon CA, Salles JE, Wajchenberg BL, Cummings DE. Effects of gastric bypass surgery in patients with type 2 diabetes and only mild obesity. Diabetes Care. 2012;35(7):1420–8.PubMedPubMedCentralCrossRefGoogle Scholar
  104. 104.
    Kenngott HG, Clemens G, Gondan M, Senft J, Diener MK, Rudofsky G, et al. DiaSurg 2 trial – surgical vs. medical treatment of insulin-dependent type 2 diabetes mellitus in patients with a body mass index between 26 and 35 kg/m2: study protocol of a randomized controlled multicenter trial – DRKS00004550. Trials. 2013;14(1):183.PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Ahren B, Schmitz O. GLP-1 receptor agonists and DPP-4 inhibitors in the treatment of type 2 diabetes. Horm Metab Res. 2004;36(11–12):867–76.PubMedCrossRefGoogle Scholar
  106. 106.
    Creutzfeldt WO, Kleine N, Willms B, Orskov C, Holst JJ, Nauck MA. Glucagonostatic actions and reduction of fasting hyperglycemia by exogenous glucagon-like peptide I(7-36) amide in type I diabetic patients. Diabetes Care. 1996;19(6):580–6.PubMedCrossRefGoogle Scholar
  107. 107.
    Delgado-Aros S, Kim DY, Burton DD, Thomforde GM, Stephens D, Brinkmann BH, et al. Effect of GLP-1 on gastric volume, emptying, maximum volume ingested, and postprandial symptoms in humans. Am J Physiol Gastrointest Liver Physiol. 2002;282(3):G424–31.PubMedGoogle Scholar
  108. 108.
    Dardevet D, Moore MC, Neal D, DiCostanzo CA, Snead W, Cherrington AD. Insulin-independent effects of GLP-1 on canine liver glucose metabolism: duration of infusion and involvement of hepatoportal region. Am J Physiol Endocrinol Metab. 2004;287(1):E75–81.PubMedCrossRefGoogle Scholar
  109. 109.
    Buse JB, Henry RR, Han J, Kim DD, Fineman MS, Baron AD, et al. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care. 2004;27(11):2628–35.PubMedCrossRefGoogle Scholar
  110. 110.
    Kendall DM, Riddle MC, Rosenstock J, Zhuang D, Kim DD, Fineman MS, et al. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea. Diabetes Care. 2005;28(5):1083–91.PubMedCrossRefGoogle Scholar
  111. 111.
    Raz I, Hanefeld M, Xu L, Caria C, Williams-Herman D, Khatami H, et al. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy in patients with type 2 diabetes mellitus. Diabetologia. 2006;49(11):2564–71.PubMedCrossRefGoogle Scholar
  112. 112.
    Charbonnel B, Karasik A, Liu J, Wu M, Meininger G, Sitagliptin Study Group. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor sitagliptin added to ongoing metformin therapy in patients with type 2 diabetes inadequately controlled with metformin alone. Diabetes Care. 2006;29(12):2638–43.PubMedCrossRefGoogle Scholar
  113. 113.
    DeFronzo RA, Hissa MN, Garber AJ, Luiz Gross J, Yuyan Duan R, Ravichandran S, et al. The efficacy and safety of saxagliptin when added to metformin therapy in patients with inadequately controlled type 2 diabetes with metformin alone. Diabetes Care. 2009;32(9):1649–55.PubMedPubMedCentralCrossRefGoogle Scholar
  114. 114.
    Del Prato S, Barnett AH, Huisman H, Neubacher D, Woerle HJ, Dugi KA. Effect of linagliptin monotherapy on glycaemic control and markers of beta-cell function in patients with inadequately controlled type 2 diabetes: a randomized controlled trial. Diabetes Obes Metab. 2011;13(3):258–67.PubMedCrossRefGoogle Scholar
  115. 115.
    Vella A, Bock G, Giesler PD, Burton DB, Serra DB, Saylan ML, et al. Effects of dipeptidyl peptidase-4 inhibition on gastrointestinal function, meal appearance, and glucose metabolism in type 2 diabetes. Diabetes. 2007;56(5):1475–80.PubMedCrossRefGoogle Scholar
  116. 116.
    Aroda VR, Henry RR, Han J, Huang W, DeYoung MB, Darsow T, et al. Efficacy of GLP-1 receptor agonists and DPP-4 inhibitors: meta-analysis and systematic review. Clin Ther. 2012;34(6):1247–58 e22.PubMedCrossRefGoogle Scholar
  117. 117.
    Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, et al. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2015;38(1):140–9.PubMedCrossRefGoogle Scholar
  118. 118.
    Kielgast U, Holst JJ, Madsbad S. Antidiabetic actions of endogenous and exogenous GLP-1 in type 1 diabetic patients with and without residual beta-cell function. Diabetes. 2011;60(5):1599–607.PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Department of Biomedical Sciences, Department of Internal MedicineCedars-Sinai Medical CenterLos AngelesUSA

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