Best Practice & Research Clinical Endocrinology & Metabolism
Volume 23, Issue 4 , Pages 413-424 , August 2009

Insulin secretion in healthy subjects and patients with Type 2 diabetes – role of the gastrointestinal tract

  • Jing Ma, MD (PhD, Student)

      Affiliations

    • University of Adelaide Discipline of Medicine, Royal Adelaide Hospital, Adelaide, SA, Australia
    • Centre of Clinical Research Excellence in Nutritional Physiology, Interventions, and Outcomes, Adelaide, SA, Australia
  • ,
  • Christopher K. Rayner, MBBS, PhD (Associate Professor)

      Affiliations

    • University of Adelaide Discipline of Medicine, Royal Adelaide Hospital, Adelaide, SA, Australia
    • Centre of Clinical Research Excellence in Nutritional Physiology, Interventions, and Outcomes, Adelaide, SA, Australia
    • Corresponding Author InformationCorresponding author. Tel.: +61 8 8222 2916; Fax: +61 8 8223 3870.
  • ,
  • Karen L. Jones, PhD (Associate Professor)

      Affiliations

    • University of Adelaide Discipline of Medicine, Royal Adelaide Hospital, Adelaide, SA, Australia
    • Centre of Clinical Research Excellence in Nutritional Physiology, Interventions, and Outcomes, Adelaide, SA, Australia
  • ,
  • Michael Horowitz, MBBS, PhD (Professor)

      Affiliations

    • University of Adelaide Discipline of Medicine, Royal Adelaide Hospital, Adelaide, SA, Australia
    • Centre of Clinical Research Excellence in Nutritional Physiology, Interventions, and Outcomes, Adelaide, SA, Australia

References 

  1. Del Prato S. In search of normoglycaemia in diabetes: controlling postprandial glucose. International Journal of Obesity and Related Metabolic Disorders. 2002;26(Suppl. 3):S9–S17
  2. Ceriello A, Hanefeld M, Leiter L, et al. Postprandial glucose regulation and diabetic complications. Archives of Internal Medicine. 2004;164:2090–2095
  3. Nathan DM, Cleary PA, Backlund JY, et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. The New England Journal of Medicine. 2005;353:2643–2653
  4. The Diabetes Control and Complications Trial Research Group . The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The New England Journal of Medicine. 1993;329:977–986
  5. UK Prospective Diabetes Study (UKPDS) Group . Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352:837–853
  6. American Diabetes Association . Postprandial blood glucose. Diabetes Care. 2001;24:775–778
  7. Perley MJ, Kipnis DM. Plasma insulin responses to oral and intravenous glucose: studies in normal and diabetic sujbjects. The Journal of Clinical Investigation. 1967;46:1954–1962
  8. Horowitz M, Nauck MA. To be or not to be–an incretin or enterogastrone?. Gut. 2006;55:148–150
  9. Deacon CF. What do we know about the secretion and degradation of incretin hormones?. Regulatory Peptides. 2005;128:117–124
  10. Drucker DJ. The biology of incretin hormones. Cell Metabolism. 2006;3:153–165
  11. Brener W, Hendrix TR, McHugh PR. Regulation of the gastric emptying of glucose. Gastroenterology. 1983;85:76–82
  12. Schirra J, Houck P, Wank U, et al. Effects of glucagon-like peptide-1 (7–36)amide on antro-pyloro-duodenal motility in the interdigestive state and with duodenal lipid perfusion in humans. Gut. 2000;46:622–631
  13. Schirra J, Nicolaus M, Roggel R, et al. Endogenous glucagon-like peptide 1 controls endocrine pancreatic secretion and antro-pyloro-duodenal motility in humans. Gut. 2006;55:243–251
  14. MacIntosh CG, Andrews JM, Jones KL, et al. Effects of age on concentrations of plasma cholecystokinin, glucagon-like peptide 1, and peptide YY and their relation to appetite and pyloric motility. The American Journal of Clinical Nutrition. 1999;69:999–1006
  15. Horowitz M, Edelbroek MA, Wishart JM, et al. Relationship between oral glucose tolerance and gastric emptying in normal healthy subjects. Diabetologia. 1993;36:857–862
  16. Jones KL, Horowitz M, Carney BI, et al. Gastric emptying in early noninsulin-dependent diabetes mellitus. Journal of Nuclear Medicine. 1996;37:1643–1648
  17. Gonlachanvit S, Hsu CW, Boden GH, et al. Effect of altering gastric emptying on postprandial plasma glucose concentrations following a physiologic meal in type-II diabetic patients. Digestive Diseases and Sciences. 2003;48:488–497
  18. Ishii M, Nakamura T, Kasai F, et al. Altered postprandial insulin requirement in IDDM patients with gastroparesis. Diabetes Care. 1994;17:901–903
  19. Olausson EA, Alpsten M, Larsson A, et al. Small particle size of a solid meal increases gastric emptying and late postprandial glycaemic response in diabetic subjects with gastroparesis. Diabetes Research and Clinical Practice. 2008;80:231–237
  20. Pilichiewicz AN, Chaikomin R, Brennan IM, et al. Load-dependent effects of duodenal glucose on glycemia, gastrointestinal hormones, antropyloroduodenal motility, and energy intake in healthy men. American Journal of Physiology. Endocrinology and Metabolism. 2007;293:E743–E753
  21. Bruce DG, Chisholm DJ, Storlien LH, et al. Physiological importance of deficiency in early prandial insulin secretion in non-insulin-dependent diabetes. Diabetes. 1988;37:736–744
  22. Gerich JE. Pathogenesis and treatment of type 2 (noninsulin-dependent) diabetes mellitus (NIDDM). Hormone and Metabolic Research. 1996;28:404–412
  23. O'Donovan DG, Doran S, Feinle-Bisset C, et al. Effect of variations in small intestinal glucose delivery on plasma glucose, insulin, and incretin hormones in healthy subjects and type 2 diabetes. The Journal of Clinical Endocrinology and Metabolism. 2004;89:3431–3435
  24. Chaikomin R, Doran S, Jones KL, 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. American Journal of Physiology. Endocrinology and Metabolism. 2005;289:E504–E507
  25. Duchman SM, Ryan AJ, Schedl HP, et al. Upper limit for intestinal absorption of a dilute glucose solution in men at rest. Medicine and Science in Sports and Exercise. 1997;29:482–488
  26. Rayner CK, Schwartz MP, van Dam PS, et al. Small intestinal glucose absorption and duodenal motility in type 1 diabetes mellitus. The American Journal of Gastroenterology. 2002;97:3123–3130
  27. Schwartz MP, Samsom M, Renooij W, et al. Small bowel motility affects glucose absorption in a healthy man. Diabetes Care. 2002;25:1857–1861
  28. Nguyen HN, Silny J, Wuller S, et al. Chyme transport patterns in human duodenum, determined by multiple intraluminal impedancometry. The American Journal of Physiology. 1995;268:G700–G708
  29. Imam H, Sanmiguel C, Larive B, et al. Study of intestinal flow by combined videofluoroscopy, manometry, and multiple intraluminal impedance. The American Journal of Physiology. Gastrointestinal and Liver Physiology. 2004;286:G263–G270
  30. Chaikomin R, Wu KL, Doran S, et al. Concurrent duodenal manometric and impedance recording to evaluate the effects of hyoscine on motility and flow events, glucose absorption, and incretin release. The American Journal of Physiology. Gastrointestinal and Liver Physiology. 2007;292:G1099–G1104
  31. Camilleri M, Malagelada JR. Abnormal intestinal motility in diabetics with the gastroparesis syndrome. European Journal of Clinical Investigation. 1984;14:420–427
  32. Samsom M, Verhagen MA. Intestinal function. In:  Horowitz M,  Samsom M editor. Gastrointestinal Function in Diabetes Mellitus. Chichester: John Wiley & Sons Ltd; 2004;p. 177–217
  33. Fujita Y, Kojima H, Hidaka H, et al. Increased intestinal glucose absorption and postprandial hyperglycaemia at the early step of glucose intolerance in Otsuka Long-Evans Tokushima fatty rats. Diabetologia. 1998;41:1459–1466
  34. Cheeseman CI, Maenz DD. Rapid regulation of D-glucose transport in basolateral membrane of rat jejunum. The American Journal of Physiology. 1989;256:G878–G883
  35. Csaky TZ, Fischer E. Induction of an intestinal epithelial sugar transport system by high blood sugar. Experientia. 1977;33:223–224
  36. Csaky TZ, Fischer E. Intestinal sugar transport in experimental diabetes. Diabetes. 1981;30:568–574
  37. Fischer E, Lauterbach F. Effect of hyperglycaemia on sugar transport in the isolated mucosa of guinea-pig small intestine. The Journal of Physiology. 1984;355:567–586
  38. Costrini NV, Ganeshappa KP, Wu W, et al. Effect of insulin, glucose, and controlled diabetes mellitus on human jejunal function. The American Journal of Physiology. 1977;233:E181–E187
  39. Gulliford MC, Bicknell EJ, Pover GG, et al. Intestinal glucose and amino acid absorption in healthy volunteers and non-insulin-dependent diabetic subjects. The American Journal of Clinical Nutrition. 1989;49:1247–1251
  40. Dyer J, Wood IS, Palejwala A, et al. Expression of monosaccharide transporters in intestine of diabetic humans. American Journal of Physiology. Gastrointestinal and Liver Physiology. 2002;282:G241–G248
  41. Schirra J, Katschinski M, Weidmann C, et al. Gastric emptying and release of incretin hormones after glucose ingestion in humans. The Journal of Clinical Investigation. 1996;97:92–103
  42. Kuo P, Chaikomin R, Pilichiewicz A, et al. Transient, early release of glucagon-like peptide-1 during low rates of intraduodenal glucose delivery. Regulatory Peptides. 2008;146:1–3
  43. Rocca AS, Brubaker PL. Role of the vagus nerve in mediating proximal nutrient-induced glucagon-like peptide-1 secretion. Endocrinology. 1999;140:1687–1694
  44. Nauck MA, Bartels E, Orskov C, et al. Additive insulinotropic effects of exogenous synthetic human gastric inhibitory polypeptide and glucagon-like peptide-1-(7–36) amide infused at near-physiological insulinotropic hormone and glucose concentrations. The Journal of Clinical Endocrinology and Metabolism. 1993;76:912–917
  45. Nauck MA, Heimesaat MM, Orskov C, et al. 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. The Journal of Clinical Investigation. 1993;91:301–307
  46. Theodorakis MJ, Carlson O, Michopoulos S, et al. Human duodenal enteroendocrine cells: source of both incretin peptides, GLP-1 and GIP. American Journal of Physiology. Gastrointestinal and Liver Physiology. 2006;290:E550–E559
  47. Little TJ, Doran S, Meyer JH, et al. The release of GLP-1 and ghrelin, but not GIP and CCK, by glucose is dependent upon the length of small intestine exposed. American Journal of Physiology. Gastrointestinal and Liver Physiology. 2006;291:E647–E655
  48. Herrmann C, Goke R, Richter G, et al. Glucagon-like peptide-1 and glucose-dependent insulin-releasing polypeptide plasma levels in response to nutrients. Digestion. 1995;56:117–126
  49. Elliott RM, Morgan LM, Tredger JA, et al. Glucagon-like peptide-1 (7–36)amide and glucose-dependent insulinotropic polypeptide secretion in response to nutrient ingestion in man: acute post-prandial and 24-h secretion patterns. The Journal of Endocrinology. 1993;138:159–166
  50. Bowen J, Noakes M, Clifton PM. Appetite regulatory hormone responses to various dietary proteins differ by body mass index status despite similar reductions in ad libitum energy intake. The Journal of Clinical Endocrinology and Metabolism. 2006;91:2913–2919
  51. Rayner CK, Park HS, Wishart JM, et al. Effects of intraduodenal glucose and fructose on antropyloric motility and appetite in healthy humans. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 2000;278:R360–R366
  52. Horowitz M, Wishart JM, Jones KL, et al. Gastric emptying in diabetes: an overview. Diabetic Medicine. 1996;13:S16–S22
  53. Frank JW, Saslow SB, Camilleri M, et al. Mechanism of accelerated gastric emptying of liquids and hyperglycemia in patients with type II diabetes mellitus. Gastroenterology. 1995;109:755–765
  54. Phillips WT, Schwartz JG, McMahan CA. Rapid gastric emptying of an oral glucose solution in type 2 diabetic patients. Journal of Nuclear Medicine. 1992;33:1496–1500
  55. Schwartz JG, Green GM, Guan D, et al. Rapid gastric emptying of a solid pancake meal in type II diabetic patients. Diabetes Care. 1996;19:468–471
  56. Jones KL, Russo A, Berry MK, et al. A longitudinal study of gastric emptying and upper gastrointestinal symptoms in patients with diabetes mellitus. The American Journal of Medicine. 2002;113:449–455
  57. Krarup T. Immunoreactive gastric inhibitory polypeptide. Endocrine Reviews. 1988;9:122–134
  58. Elahi D, McAloon-Dyke M, Fukagawa NK, et al. The insulinotropic actions of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (7–37) in normal and diabetic subjects. Regulatory Peptides. 1994;51:63–74
  59. Vilsboll T, Krarup T, Madsbad S, et al. Defective amplification of the late phase insulin response to glucose by GIP in obese type II diabetic patients. Diabetologia. 2002;45:1111–1119
  60. Lynn FC, Pamir N, Ng EH, et al. Defective glucose-dependent insulinotropic polypeptide receptor expression in diabetic fatty Zucker rats. Diabetes. 2001;50:1004–1011
  61. Meier JJ, Hucking K, Holst JJ, et al. Reduced insulinotropic effect of gastric inhibitory polypeptide in first-degree relatives of patients with type 2 diabetes. Diabetes. 2001;50:2497–2504
  62. Vilsboll T, Knop FK, Krarup T, et al. The pathophysiology of diabetes involves a defective amplification of the late-phase insulin response to glucose by glucose-dependent insulinotropic polypeptide-regardless of etiology and phenotype. The Journal of Clinical Endocrinology and Metabolism. 2003;88:4897–4903
  63. Toft-Nielsen MB, Damholt MB, Madsbad S, et al. Determinants of the impaired secretion of glucagon-like peptide-1 in type 2 diabetic patients. The Journal of Clinical Endocrinology and Metabolism. 2001;86:3717–3723
  64. Chandalia M, Garg A, Lutjohann D, et al. Beneficial effects of high dietary fiber intake in patients with type 2 diabetes mellitus. The New England Journal of Medicine. 2000;342:1392–1398
  65. Russo A, Stevens JE, Wilson T, et al. Guar attenuates fall in postprandial blood pressure and slows gastric emptying of oral glucose in type 2 diabetes. Digestive Diseases and Sciences. 2003;48:1221–1229
  66. Cunningham KM, Read NW. The effect of incorporating fat into different components of a meal on gastric emptying and postprandial blood glucose and insulin responses. The British Journal of Nutrition. 1989;61:285–290
  67. Feinle C, O'Donovan D, Doran S, et al. Effects of fat digestion on appetite, APD motility, and gut hormones in response to duodenal fat infusion in humans. American Journal of Physiology. Gastrointestinal and Liver Physiology. 2003;284:G798–G807
  68. O'Donovan D, Horowitz M, Russo A, et al. Effects of lipase inhibition on gastric emptying of, and on the glycaemic, insulin and cardiovascular responses to, a high-fat/carbohydrate meal in type 2 diabetes. Diabetologia. 2004;47:2208–2214
  69. Gentilcore D, Chaikomin R, Jones KL, et al. Effects of fat on gastric emptying of, and the glycemic, insulin and incretin responses to, a carbohydrate meal in type 2 diabetes. The Journal of Clinical Endocrinology and Metabolism. 2006;91(6):2062–2067
  70. Thompson RG, Pearson L, Kolterman OG. Effects of 4 weeks' administration of pramlintide, a human amylin analogue, on glycaemia control in patients with IDDM: effects on plasma glucose profiles and serum fructosamine concentrations. Diabetologia. 1997;40:1278–1285
  71. Thompson RG, Pearson L, Schoenfeld SL, et al. Pramlintide, a synthetic analog of human amylin, improves the metabolic profile of patients with type 2 diabetes using insulin. The Pramlintide in type 2 diabetes group. Diabetes Care. 1998;21:987–993
  72. Singh-Franco D, Robles G, Gazze D. Pramlintide acetate injection for the treatment of type 1 and type 2 diabetes mellitus. Clinical Therapeutics. 2007;29:535–562
  73. Aronne L, Fujioka K, Aroda V, et al. Progressive reduction in body weight after treatment with the amylin analog pramlintide in obese subjects: a phase 2, randomized, placebo-controlled, dose-escalation study. The Journal of Clinical Endocrinology and Metabolism. 2007;92:2977–2983
  74. Nauck MA, Niedereichholz U, Ettler R, et al. Glucagon-like peptide 1 inhibition of gastric emptying outweighs its insulinotropic effects in healthy humans. The American Journal of Physiology. 1997;273:E981–E988
  75. Little TJ, Pilichiewicz AN, Russo A, et al. Effects of intravenous glucagon-like peptide-1 on gastric emptying and intragastric distribution in healthy subjects: relationships with postprandial glycemic and insulinemic responses. The Journal of Clinical Endocrinology and Metabolism. 2006;91:1916–1923
  76. Cervera A, Wajcberg E, Sriwijitkamol A, et al. Mechanism of action of exenatide to reduce postprandial hyperglycemia in type 2 diabetes. American Journal of Physiology. Endocrinology and Metabolism. 2008;294:E846–E852
  77. Bischoff H. Pharmacology of alpha-glucosidase inhibition. European Journal of Clinical Investigation. 1994;24(Suppl. 3):3–10
  78. Qualmann C, Nauck MA, Holst JJ, et al. Glucagon-like peptide 1 (7–36 amide) secretion in response to luminal sucrose from the upper and lower gut. A study using alpha-glucosidase inhibition (acarbose). Scandinavian Journal of Gastroenterology. 1995;30:892–896
  79. Ranganath L, Norris F, Morgan L, et al. Delayed gastric emptying occurs following acarbose administration and is a further mechanism for its anti-hyperglycaemic effect. Diabetic Medicine. 1998;15:120–124
  80. Hucking K, Kostic Z, Pox C, et al. Alpha-Glucosidase inhibition (acarbose) fails to enhance secretion of glucagon-like peptide 1 (7–36 amide) and to delay gastric emptying in type 2 diabetic patients. Diabetic Medicine. 2005;22:470–476
  81. Mourot J, Thouvenot P, Couet C, et al. Relationship between the rate of gastric emptying and glucose and insulin responses to starchy foods in young healthy adults. The American Journal of Clinical Nutrition. 1988;48:1035–1040
  82. Ou S, Kwok K, Li Y, et al. In vitro study of possible role of dietary fiber in lowering postprandial serum glucose. Journal of Agricultural and Food Chemistry. 2001;49:1026–1029
  83. Bjorck I, Elmstahl HL. The glycaemic index: importance of dietary fibre and other food properties. The Proceedings of the Nutrition Society. 2003;62:201–206
  84. Drucker DJ. The role of gut hormones in glucose homeostasis. The Journal of Clinical Investigation. 2007;117:24–32
  85. Fineman MS, Bicsak TA, Shen LZ, et al. Effect on glycemic control of exenatide (synthetic exendin-4) additive to existing metformin and/or sulfonylurea treatment in patients with type 2 diabetes. Diabetes Care. 2003;26:2370–2377
  86. Ahren B. DPP-4 inhibitors. Best Practice & Research. Clinical Endocrinology & Metabolism. 2007;21:517–533
  87. Charbonnel B, Karasik A, Liu J, et al. 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;29:2638–2643
  88. Woerle HJ, Lindenberger T, Linke R, et al. A single dose of vildagliptin decelerates gastric emptying in patients with type 2 diabetes (Abstract). 67th Scientific Sessions of the American Diabetes Association. 2007;500-P
  89. Vella A, Bock G, Giesler PD, et al. Effects of dipeptidyl peptidase-4 inhibition on gastrointestinal function, meal appearance, and glucose metabolism in type 2 diabetes. Diabetes. 2007;56:1475–1480
  90. Gutierrez M, Akhavan M, Jovanovic L, et al. Utility of a short-term 25% carbohydrate diet on improving glycemic control in type 2 diabetes mellitus. Journal of the American College of Nutrition. 1998;17:595–600
  91. Stern L, Iqbal N, Seshadri P, et al. The effects of low-carbohydrate versus conventional weight loss diets in severely obese adults: one-year follow-up of a randomized trial. Annals of Internal Medicine. 2004;140:778–785
  92. Wolever TM. Relationship between dietary fiber content and composition in foods and the glycemic index. The American Journal of Clinical Nutrition. 1990;51:72–75
  93. Gannon MC, Nuttall FQ, Saeed A, et al. An increase in dietary protein improves the blood glucose response in persons with type 2 diabetes. The American Journal of Clinical Nutrition. 2003;78:734–741
  94. Gannon MC, Nuttall FQ, Neil BJ, et al. The insulin and glucose responses to meals of glucose plus various proteins in type II diabetic subjects. Metabolism. 1988;37:1081–1088
  95. Karamanlis A, Chaikomin R, Doran S, et al. Effects of protein on glycemic and incretin responses and gastric emptying after oral glucose in healthy subjects. The American Journal of Clinical Nutrition. 2007;86:1364–1368
  96. Gunnarsson PT, Winzell MS, Deacon CF, et al. Glucose-induced incretin hormone release and inactivation are differently modulated by oral fat and protein in mice. Endocrinology. 2006;147:3173–3180
  97. Ma J, Stevens JE, Maddox AF, et al. Effect of a protein preload on gastric emptying and glycaemia in type 2 diabetes (Abstract). Gastroenterology. 2008;134:A247–A248
  98. Chaikomin R, Rayner CK, Jones KL, et al. Upper gastrointestinal function and glycemic control in diabetes mellitus. World Journal of Gastroenterology. 2006;12:5611–5621

PII: S1521-690X(09)00028-1

doi: 10.1016/j.beem.2009.03.009

Best Practice & Research Clinical Endocrinology & Metabolism
Volume 23, Issue 4 , Pages 413-424 , August 2009