Impact of incretin therapy on islet dysfunction: An underlying defect in the pathophysiology of type 2 diabetes

Postgraduate Medicine

Volumn 121, Issue 1, 2009, Pages 46-58

  McGill, Janet B ^a  

^a WASHINGTON UNIVERSITY   (United States)

Author keywords

Alpha cell; Beta cell; DPP 4; Exenatide; GLP 1 analog; Human; Islet dysfunction; Liraglutide; Once daily; Type 2 diabetes mellitus

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; AMYLIN; DIPEPTIDYL PEPTIDASE IV INHIBITOR; EXENDIN 4; GASTRIC INHIBITORY POLYPEPTIDE; GLIMEPIRIDE; GLUCAGON; GLUCAGON LIKE PEPTIDE 1; GLUCOSE; HEMOGLOBIN A1C; HORMONE; INCRETIN; INSULIN; LIRAGLUTIDE; METFORMIN; PLACEBO; PRAMLINTIDE; SAXAGLIPTIN; SITAGLIPTIN; SULFONYLUREA; VILDAGLIPTIN; ANTIDIABETIC AGENT; GLUCAGON LIKE PEPTIDE RECEPTOR; GLUCAGON RECEPTOR; GLUCAGON-LIKE PEPTIDE RECEPTOR;

ADD ON THERAPY; CELL FUNCTION; CLINICAL TRIAL; DIABETES MELLITUS; DIET RESTRICTION; DISEASE COURSE; DRUG APPROVAL; DRUG BINDING; DRUG DOSE TITRATION; DRUG EFFICACY; DRUG HALF LIFE; DRUG TARGETING; EVALUATION; GENETIC SUSCEPTIBILITY; GLUCOSE BLOOD LEVEL; GLUCOSE HOMEOSTASIS; GLUCOSE METABOLISM; HUMAN; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PANCREAS ISLET; PANCREAS ISLET BETA CELL; PROTEIN INTERACTION; REVIEW; ARTICLE; DRUG EFFECT; DRUG POTENTIATION; FEMALE; MALE; METABOLISM; PATHOPHYSIOLOGY; PHYSIOLOGY; SECRETION;

DIABETES MELLITUS, TYPE 2; DIPEPTIDYL-PEPTIDASE IV INHIBITORS; FEMALE; GLUCOSE; HUMANS; HYPOGLYCEMIC AGENTS; INCRETINS; INSULIN; ISLETS OF LANGERHANS; MALE; RECEPTORS, GLUCAGON;

EID: 60549093417     PISSN: 00325481     EISSN: 19419260     Source Type: Journal    
DOI: 10.3810/pgm.2009.01.1954     Document Type: Review

References (135)

1. Pratley RE, Weyer C. The role of impaired early insulin secretion in the pathogenesis of Type II diabetes mellitus. Diabetologia. 2001;44(8):929-945. (Pubitemid 32778125)
2. Weyer C, Bogardus C, Mott DM, Pratley RE. The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus. J Clin Invest. 1999;104(6):787-794. (Pubitemid 29536364)
3. DeFronzo RA. Pathogenesis of type 2 diabetes mellitus. Med Clin North Am. 2004;88(4):787-835. (Pubitemid 39090340)
4. Buchanan TA, Xiang AH, Peters RK, et al. Preservation of pancreatic beta-cell function and prevention of type 2 diabetes by pharmacological treatment of insulin resistance in high-risk Hispanic women. Diabetes. 2002;51(9):2796-2803. (Pubitemid 34970933)
5. Young A. Inhibition of glucagon secretion. Adv Pharmacol. 2005; 52:151-171.
6. Dunning BE, Gerich JE. The role of alpha-cell dysregulation in fasting and postprandial hyperglycemia in type 2 diabetes and therapeutic implications. Endocr Rev. 2007;28(3):253-283. (Pubitemid 46984828)
7. Aronoff SL, Berkowitz K, Shreiner B, Want L. Glucose metabolism and regulation: beyond insulin and glucagon. Diabetes Spectrum. 2004;17(4):183-1109
8. Moore CX, Cooper GJ. Co-secretion of amylin and insulin from cultured islet beta-cells: modulation by nutrient secretagogues, islet hormones and hypoglycemic agents. Biochem Biophys Res Commun. 1991;179(1):1-9.
9. Baggio LL, Drucker DJ. Biology of incretins: GLP-1 and GIP. Gastroenterology. 2007;132(6):2131-2157. (Pubitemid 46711096)
10. Bock G, Dalla Man C, Campioni M, et al. Pathogenesis of pre-diabetes: mechanisms of fasting and postprandial hyperglycemia in people with impaired fasting glucose and/or impaired glucose tolerance. Diabetes. 2006;55(12):3536-3549. (Pubitemid 44923615)
11. Eriksson J, Franssila-Kallunki A, Ekstrand A, et al. Early metabolic defects in persons at increased risk for non-insulin-dependent diabetes mellitus. N Engl J Med. 1989;321(6):337-343. (Pubitemid 19190437)
12. Holman RR. Assessing the potential for alpha-glucosidase inhibitors in prediabetic states. Diabetes Res Clin Pract. 1998;40(suppl): S21-S25. (Pubitemid 28370886)
13. Butler AE, Janson J. Bonner-Weir S, Ritzel R, Rizza RA, Butler PC. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes. 2003;52(1):102-110. (Pubitemid 36042113)
14. Bagust A, Beale S. Deteriorating beta-cell function in type 2 diabetes: a long-term model. QJM. 2003;96(4):281-288. (Pubitemid 36432387)
15. U.K. Prospective Diabetes Study Group. U.K. prospective diabetes study 16. Overview of 6 years' therapy of type II diabetes: a progressive disease. Diabetes. 1995;44(11):1249-1258.
16. Gerich JE, Schneider V, Dippe SE, et al, Characterization of the glucagon response to hypoglycemia in man. J Clin Endocrinol Metab. 1974;38(1):77-82.
17. Weir GC, Bonner-Weir S. Five stages of evolving beta-cell dysfunction during progression to diabetes. Diabetes. 2004;53(suppl 3):S16-S21. (Pubitemid 39564517)
18. Hanson RL, Imperatore G, Narayan KM, et al, Family and genetic studies of indices of insulin sensitivity and insulin secretion in Pima Indians. Diabetes Metab Res Rev. 2001;17(4):296-303. (Pubitemid 32821662)
19. Henkin L, Bergman RN, Bowden DW, et al. Genetic epidemiology of insulin resistance and visceral adiposity. The IRAS family Study design and methods. Ann Epidemiol. 2003;13(4):211-217. (Pubitemid 36390342)
20. Permutt MA, Wasson J, Cox N. Genetic epidemiology of diabetes. J Clin Invest. 2005;115(6):1431-1439. (Pubitemid 40814647)
21. Colditz GA, Willelt WC, Rotnitzky A, Manson JE. Weight gain as a risk factor for clinical diabetes mellitus in women. Ann Intern Med. 1995;122(7):481-486.
22. Field AE, Coakley EU, Must A, et al. Impact of overweight on the risk of developing common chronic diseases during a 10-year period. Arch Intern Med. 2001;161(13):1581-1586. (Pubitemid 32681139)
23. Hart CL, Hole DJ, Lawlor DA, Davey Smith G. How many cases of Type 2 diabetes mellitus are due to being overweight in middle age? Evidence from the Midspan prospective cohort studies using mention of diabetes mellitus on hospital discharge or death records. Diabet Med. 2007;24(1):73-80. (Pubitemid 46103074)
24. Hossain P, Kawar B, El Nabas M. Obesity and diabetes in the developing world - a growing challenge. N Engl J Med. 2007;356;(3):213-215. (Pubitemid 46143224)
25. Narayan KM, Boyle JP, Thompson TJ, Gregg EW, Williamson DF. Effect of BMI on lifetime risk for diabetes in the U.S. Diabetes Care. 2007;30(6):1562-1566. (Pubitemid 46871171)
26. Wannamethee SG, Shaper AG, Walker M. Overweight and obesity and weight change in middle aged men: impact on cardiovascular disease and diabetes. J Epidemiol Community Health. 2005;59(2):134-139. (Pubitemid 40139326)
27. Fujimoto WY, Bergstrom RW, Boyko EJ, et al. Type 2 diabetes and the metabolic syndrome in Japanese Americans. Diabetes Res Clin Pract. 2000;50(suppl 2):S73-S76.
28. Turner RC, Cull CA, Frighi V, Holman RR. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group. JAMA. 1999;281(21):2005-2012. (Pubitemid 29254858)
29. Bonora E. Protection of pancreatic beta-cells: is it feasible? Nutr Metab Cardiovasc Dis. 2008;18(1):74-83. (Pubitemid 50020512)
30. Ahren B, Pacini G, Foley JE, Schweizer A. Improved meal-related beta-cell function and insulin sensitivity by the dipeptidyl peptidase-IV inhibitor vildagliptin in metformin-treated patients with type 2 diabetes over 1 year. Diabetes Care. 2005;28(8):1936-1940. (Pubitemid 41060966)
31. Aschner P, Kipnes MS, Lunceford JK, Sanchez M, Mickel C, Williams-Herman DE; Sitagliptin Study 021 Group. Effect of the dipeptidyl peptidase-4 inhibitor sitagliptin as monotherapy on glycemic control in patients with type 2 diabetes. Diabetes Care. 2006; 29(12):2632-2637. (Pubitemid 44912190)
32. Balas B, Baig MR, Watson C, et al. The dipeptidyl peptidase IV inhibitor vildagliptin suppresses endogenous glucose production and enhances islet function after single-dose administration in type 2 diabetic patients. J Clin Endocrinol Metab. 2007;92(4):1249-1255. (Pubitemid 46556394)
33. Bock T, Pakkenberg B, Buschard K. The endocrine pancreas in non- diabetic rats after short-term and long-term treatment with the long- acting GLP-1 derivative NN2211. APMIS. 2003;111(12):1117-1124. (Pubitemid 38091251)
34. Bregenholt S, Moldrup A, Blume N, et al. The long-acting glucagon- like peptide-1 analogue, liraglutide, inhibits beta-cell apoptosis in vitro. Biochem Biophys Res Commun. 2005;330(2):577-584. (Pubitemid 40417684)
35. Charbonnel B, Karasik A, Liu J, Wu M, Meininger G; Sitagliptin Study 020 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):2638-2643. (Pubitemid 44912191)
36. Chen J, Couto FM, Minn AH, Shalev A. Exenatide inhibits beta-cell apoptosis by decreasing thioredoxin-intcracting protein. Biochem Biophys Res Commun. 2006;346(3):1067-1074. (Pubitemid 43913716)
37. Degn KB, Juhl CB, Sturis J, et al. One week's treatment with the long- acting glucagon-like peptide 1 derivative liraglutide (NN2211) markedly improves 24-h glycemic and alpha- and beta-cell function and reduces endogenous glucose release in patients with type 2 diabetes. Diabetes. 2004;53(5):1187-1194. (Pubitemid 38569002)
38. Del Guerra S, Marselli L, Lupi R, et al. Effects of prolonged in vitro exposure in sulphonylureas on the function and survival of human islets. J Diabetes Complications. 2005;19(1):60-64. (Pubitemid 40092372)
39. Efanova IB, Zaitsev SV, Zhivotovsky B, et al. Glucose and tolbutamide induce apoptosis in pancreatic beta-cells. A process dependent on intracellular Ca2+ concentration. J Biol Chem. 1998;273(50):33501-33507. (Pubitemid 129754428)
40. Finegood DT, McArthur MD, Kojwang D, et al. Beta-cell mass dynamics in Zucker diabetic fatty rats. Rosiglitazone prevents the rise in net cell death. Diabetes. 2001;50(5):1021-1029. (Pubitemid 32374532)
41. Fineman M, Weyer C, Maggs DG, Strubel S, Kolterman OG. The human amylin analog, pramlintide, reduces postprandial hyperglucagonemia in patients with type 2 diabetes mellitus. Horm Metab Res. 2002;34(9):504-508. (Pubitemid 35192237)
42. Gedulin BR, Nikoulina SE, Smith PA, et al. Exenatide (exendin-4) improves insulin sensitivity and (beta)-cell mass in insulin-resistant obese fa/fa Zucker rats independent of glycemia and body weight. Endocrinology. 2005;146(4):2069-2076. (Pubitemid 40396918)
43. DREAM (Diabetes REduction Assessment with ramipril and rosiglitazone Medication) Trial Investigators; Gerstein HC, Yusuf S, Bosch J, et al. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet. 2006;368(9541):1096-1105.
44. Ishida H, Takizawa M, Ozawa S, et al. Pioglitazone improves insulin secretory capacity and prevents the loss of beta-cell mass in obese diabetic db/db mice: Possible protection of beta cells from oxidative stress. Metabolism. 2004;53(4):488-494. (Pubitemid 38419193)
45. Juhl CB, Hollingdal M, Sturis J, et al. Bedtime administration of NN2211, a long-acting GLP-1 derivative, substantially reduces fasting and post- prandial glycemia in type 2 diabetes. Diabetes. 2002;51(2):424-429. (Pubitemid 34764798)
46. Kolterman OG, Buse JB, Fineman MS, et al. Synthetic exendin-4 (exenatide) significantly reduces postprandial and fasting plasma glucose in subjects with type 2 diabetes. J Clin Endocrinol Metab. 2003;88(7):3082-3089. (Pubitemid 36877476)
47. Maedler K, Carr RD, Bosco D, Zuellig RA, Berney T, Donath MY, Sulfonylurea induced beta-cell apoptosis in cultured human islets. J Clin Endocrinol Metab. 2005;90(1):501-506. (Pubitemid 40116700)
48. Matthews D, Marre M, Le-Thi T, Zdravkovic M, Simo R. Liraglutide, a once-daily human GLP-1 analog, significantly improves β-cell function in subjects with type 2 diabetes. In: 68th Scientific Sessions of the American Diabetes Association: June 6-10, 2008; San Francisco, CA.
49. Nyholm B, Orskov L, Hove KY, et al. The amylin analog pramlintide improves glycemic control and reduces postprandial glucagon concentrations in patients with type 1 diabetes mellitus. Metabolism. 1999;48(7):935-941. (Pubitemid 29310053)
50. Rolin B, Larsen MO, Gotfredsen CF, et al. The long-acting GLP-1 derivative NN2211 ameliorates glycemia and increases beta-cell mass in diabetic mice. Am J Physiol Endocrinol Metab. 2002;283(4):E745-E752. (Pubitemid 35050813)
51. Rosenblatt S, Miskin B, Glazer NB, Prince MJ, Robertson KE; Pioglitazone 026 Study Group. The impact of pioglitazone on glycemic control and atherogenic dyslipidemia in patients with type 2 diabetes mellitus. Coron Artery Dis. 2001;12(5):413-423. (Pubitemid 32664824)
52. Sturis J, Gotfredsen CF, Remer J, et al. GLP-1 derivative liraglutide in rats with beta-cell deficiencies: influence of metabolic state on beta-cell mass dynamics. Br J Pharmacol. 2003;140(1):123-132. (Pubitemid 37175838)
53. Tan MH, Baksi A, Krahulec B, et al; GLAL Study Group. Comparison of pioglitazone and gliclazide in sustaining glycemic control over 2 years in patients with type 2 diabetes. Diabetes Care. 2005;28(3):544-550. (Pubitemid 40315311)
54. Utzschneider KM, Tong J, Montgomery B, et al. The dipeptidyl peptidase-4 inhibitor vildagliptin improves beta-cell function and insulin sensitivity in subjects with impaired fasting glucose. Diabetes Care. 2008;31(1):108-113.
55. Wallace TM, Levy JC, Matthews DR. An increase in insulin sensitivity and basal beta-cell function in diabetic subjects treated with pioglitazone in a placebo-controlled randomized study. Diabet Med. 2004;21(6):568-576. (Pubitemid 38746276)
56. 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):2270-2276. (Pubitemid 30395416)
57. Vilsbøll T, Brock B, Perrild H, et al. Liraglutide, a once-daily human GLP-1 analogue, improves pancreatic B-cell function and arginine- stimulaled insulin secretion during hyperglycaemia in patients with Type 2 diabetes mellitus. Diabet Med. 2008;25(2):152-156.
58. Mu J, Woods J, Zhou YP, et al. Chronic inhibition of dipeptidyl peptidase-4 with a sitagliptin analog preserves pancreatic beta-cell mass and function in a rodent model of type 2 diabetes. Diabetes. 2006;55(6):1695-1704. (Pubitemid 44324122)
59. Mari A, Degn K, Brock B, Rungby J, Ferrannini E, Schmitz O. Effects of the long-acting human glucagon-like peptide-1 analog liraglutide on beta-cell function in normal living conditions. Diabetes Care. 2007;30(8):2032-2033. (Pubitemid 47219415)
60. Actos® (pioglitazone hydrochloride tablets) [package insert]. Lincolnshire, IL and Indianapolis, IN: Takeda Pharmaceuticals America, Inc and Eli Lilly and Co; 2002. http://www.fda.gov/medwatch/SAFETY/2003/03Jan-labels/ Actos-PI.pdf. March 2002.
61. Amaryl® (glimepiride tablets) [package insert]. Bridge water, NJ: Aventis Pharmaceuticals Inc; 2005. http://www.fda.gov/medWatch/safety/2005/Nov- PI/Amaryl-PI.pdf. October 2005.
62. Avandia® (rosiglitazone) [package insert]. Boronia, Victoria: GlaxoSmithKline Australia Ply Ltd; 2008. http://www.gsk.com.au/ resources.ashx/prescriptionmedicinesproductschilddataproinfo/515/F ileName/1270CD65C97D606551EDBA1AEFA19F9C/PI-Avandia. pdf. October 2008.
63. Berria R, Gastaldelli M, Nauck M, Boldrin M, Asnaghi V, Balena R. Eight weeks treatment with R1583, a novel long-acting, human GLP-1 analogue improves beta cell Function in metformin-trealed diabetic subjects: a double-blind, placebo-controlled phase 2 study. In: 44th Annual Meeting of the EASD European Association for the Study of Diabetes; September 7-11, 2008; Rome, Italy.
64. Byetta® (exenatide injection) [package insert]. San Diego, CA: Amylin Pharmaceuticals, Inc; 2008. http://pi.lilly.com/us/byetta-pi.pdf. June 2008.
65. Galvus® (vildagliptin). Summary of Products Characteristics. Nuremberg, Germany: Novartis Pharma. http://www.emea.europa.eu/humandocs/ PDFs/EPAR/galvus/H-771-PI-en.pdf.
66. Garber A, Henry R, Ratner R, et al; for the LEAD-3 (Mono) Study Group. Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial [published online ahead of print September 24, 2008]. Lancet.
67. Januvia™ (sitagliptin tablets) [package insert]. Whitehouse Station, NJ: Merck and Co, Inc; 2007. http://www.merck.com/product/usa/pi- circulars/j/januvia/januvia-pi.pdf.
68. Kahn SE, Zinman B, Lachin JM, et al; Diabetes Outcome Progression Trial (ADOPT) Study Group. Rosiglitazone-associated fractures in type 2 diabetes: an Analysis from A Diabetes Outcome Progression Trial (ADOPT). Diabetes Care. 2008;31(5):845-851.
69. Micronase® (glyburide tablets) [package insert]. New York, NY: Pfizer, Inc; 2006. http://www.pfizer.com/files/products/uspi-micronase.pdf. June 2006.
70. Moritoh Y, Takeuchi K, Asakawa T, Kataoka O, Odaka H. Chronic administration of alogliptin, a novel, potent, and highly selective dipeptidyl peptidase-4 inhibitor, improves glycemic control and beta-cell function in obese diabetic ob/ob mice. Eur J Pharmacol. 2008;588(2-3):325-332.
71. Nauck M, Frid A, Hermansen K, et al; for the LEAD-2 Metformin Study Group. Efficacy and safety comparison of liraglutide, glimepiride, and placebo, all in combination with metformin in type 2 diabetes mellitus (LEAD-2 Met) [published online ahead of print October 17, 2008]. Diabetes Care.
72. Novo Nordisk. Liraglutide press release. http://press.novonordisk- us.com/internal.aspx?rid=437. Updated October 17, 2008. Accessed December 12, 2008.
73. Symlin® (pramlintide acetate) injection [package insert]. Amylin Pharmaceuticals, Inc: San Diego, CA; 2008. https://www.symlin. com/pdf/SYMLIN-pi-combined.pdf. July 2008.
74. Werner U, Vandewalle B, Kerr Conte J, Pattou F, Pruniax M-P, Herling AW. The GLP-1 receptor agonist AVE0010 improves GSIS, prevents lipotoxicity-induced insulin depletion and preserves beta-cell function in human pancreatic islets. In: 68th Scientific Sessions of the American Diabetes Association; June 6-10, 2008; San Francisco, CA.
75. Decker M, Hofflich H, Elias AN. Thiazolidinediones and the preservation of beta-cell function, cellular proliferation and apoptosis. Diabetes Obes Metab. 2008;10(8):617-625.
76. Dormandy JA, Charbonnel B, Eckland DJ, et al; PROactive investigators. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspectivc pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet. 2005;366(9493):1279-1289. (Pubitemid 41416583)
77. Hennansen K, Mortensen LS. Bodyweight changes associated with antihyperglycaemic agents in type 2 diabetes mellitus. Drug Saf. 2007;30(12):1127-1142. (Pubitemid 350172854)
78. Kahn SE, Haffner SM, Heise MA, et al; ADOPT Study Group. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med. 2006;355(23):2427-2443.
79. Amori RE, Lau J, Pittas AG. Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and meta-analysis. JAMA. 2007;298(2):194-206. (Pubitemid 47057766)
80. Avandia® (rosiglitazone maleate) [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2008.
81. Deacon CF, Holst JJ. Dipeptidyl peptidase IV inhibitors: a promising new therapeutic approach for (he management of type 2 diabetes. Int J Biochem Cell Biol. 2006;38(5-6):831-844. (Pubitemid 43363415)
82. Holst JJ, Deacon CF. Glucagon-like peptide I and inhibitors of dipeptidyl peptidase IV in the treatment of type 2 diabetes mellitus. Curr Opin Pharmacol. 2004;4(6):589-596. (Pubitemid 40276776)
83. Polonsky KS, Given BD, Van Cauter E. Twenty-four-hour profiles and pulsatile patterns of insulin secretion in normal and obese subjects. J Clin Invest. 1988;81(2):442-448. (Pubitemid 18075238)
84. Cherrington AD, Sindelar D, Edgerton D, Steiner K, McGuinness OP. Physiological consequences of phasic insulin release in the normal animal. Diabetes. 2002;51(suppl 1):S103-S108. (Pubitemid 34761503)
85. Cavaghan MK, Ehrmann DA, Polonsky KS. Interactions between insulin resistance and insulin secretion in the development of glucose intolerance. J Clin Invest. 2000;106(3):329-333. (Pubitemid 30655631)
86. 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):301-307. (Pubitemid 23037285)
87. Pratley R. Islet dysfunction: an underlying defect in the pathophysiology of type 2 diabetes. Endocrinol Metab Clin North Am. 2006;35(suppl 1):6-11. (Pubitemid 46561193)
88. Lugari R, Dei Cas A, Ugolotti D, et al. Evidence for early impairment of glucagon-like peptide 1-induced insulin secretion in human type 2 (non insulin-dependent) diabetes. Horm Metab Res. 2002;34(3):150-154. (Pubitemid 34293273)
89. Vilsbøll T, Krarup T, Deacon CF, Madsbad S, Holst JJ. Reduced postprandial concentrations of intact biologically active glucagon-like peptide I in type 2 diabetic patients. Diabetes. 2001;50(3):609-613. (Pubitemid 32195226)
90. Robertson RP, Harmon J, Tran PO, Poitout V. Beta-cell glucose toxicity, lipotoxicity, and chronic oxidative stress in type 2 diabetes. Diabetes. 2004;53(suppl 1):S119-S124. (Pubitemid 38168703)
91. Biarnés M, Montolio M, Nacher V, Raurell M, Soler I, Montanya E. Beta-cell death and mass in syngeneically transplanted islets exposed to short- and long-term hyperglycemia. Diabetes. 2002;51(1):66-72. (Pubitemid 34517981)
92. Bays H, Mandarino L, DeFronzo RA. Role of the adipocyte, free fatty acids, and ectopic fat in pathogenesis of type 2 diabetes mellitus: peroxisomal proliferator-activated receptor agonists provide a rational therapeutic approach. J Clin Endocrinol Metab. 2004;89(2):463-478. (Pubitemid 38269844)
93. Cooper GJ, Willis AC, Clark A, Turner RC, Sim RB, Reid KB. Purification and characterization of a peptide from amyloid-rich pancreases of type 2 diabetic patients. Proc Natl Acad Sci U S A. 1987;84(23):8628-8632. (Pubitemid 18033465)
94. Mather KJ, Paradisi G, Leaming R, et al. Role of amylin in insulin secretion and action in humans: antagonist studies across the spectrum of insulin sensitivity. Diabetes Metab Res Rev. 2002;18(2):118-126. (Pubitemid 34467301)
95. Kahn SE. The importance of the beta-cell in the pathogenesis of type 2 diabetes mellitus. Am J Med. 2000;108(suppl 6a):2S-8S. (Pubitemid 30190142)
96. Maruyama H, Hisatomi A, Orci L, Grodsky GM, Unger RH. Insulin within islets is a physiologic glucagon release inhibitor. J Clin Invest. 1984;74(6):2296-2299. (Pubitemid 15197376)
97. Müller WA, Faloona GR, Aguilar-Parada E, Unger RH. Abnormal alpha-cell function in diabetes. Response to carbohydrate and protein ingestion. N Engl J Med. 1970;283(3):109-115.
98. Lefebvre PJ. Alpha-cell function in type 2 diabetes. Eur Endocrin Dis. 2006;41-42.
99. Rahier J, Goebbels RM, Henquin JC. Cellular composition of the human diabetic pancreas. Diabetologia. 1983;24(5):366-371.
100. Göke B. Islet cell function: alpha and beta cells - partners towards normoglycaemia. Int J Clin Pract Suppl. 2008;(159):2-7.
101. Knudsen LB, Nielsen PF, Huusfeldt PO, et al. Potent derivatives of glucagon-like peptide-1 with pharmacokinetic properties suitable for once daily administration. J Med Chem. 2000;43(9): 1664-1669. (Pubitemid 30304999)
102. Meier JJ. Beta cell mass in diabetes: a realistic therapeutic target? Diabetologia. 2008;51(5):703-713.
103. Abdul-Ghani MA, Tripathy D, DeFronzo RA. Contributions of beta-cell dysfunction and insulin resistance to the pathogenesis of impaired glucose tolerance and impaired fasting glucose. Diabetes Care. 2006;29(5):1130-1139. (Pubitemid 44115261)
104. Festa A, Williams K, Hanley AJ, Haffner SM. Beta-cell dysfunction in subjects with impaired glucose tolerance and early type 2 diabetes. Comparison of surrogate markers with first phase insulin secretion from an intravenous glucose tolerance test. Diabetes. 2008;57(6):1638-1644.
105. The DCCT Research Group. Weight gain associated with intensive therapy in the diabetes control and complications trial. Diabetes Care. 1988;11(7):567-573. (Pubitemid 18191803)
106. Nikolaidis LA, Mankad S, Sokos GG, et al. Effects of glucagon- like peptide-1 in patients with acute myocardial infarction and left ventricular dysfunction after successful reperfusion. Circulation. 2004;109(8):962-965. (Pubitemid 38282847)
107. Nikolaidis LA, Doverspike A, Hentosz T, et al. Glucagon-like peptide-1 limits myocardial stunning following brief coronary occlusion and reperfusion in conscious canines. J Pharmacol Exp Ther. 2005;312(1):303-308. (Pubitemid 40096482)
108. Mentlein R, Gallwitz B, Schmidt WE. Dipeptidyl-peptidase IV hydrolyses gastric inhibitory polypeptide, glucagon-like peptide-1 (7-36)amide, peptide histidine methionine and is responsible for their degradation in human serum. Eur J Biochem. 1993;214(3): 829-835. (Pubitemid 23188160)
109. Buse JB, Henry RR, Han J, Kim DD, Fineman MS, Baron AD; Exenatide-113 Clinical Study Group. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care. 2004;27(11):2628-2635. (Pubitemid 39441462)
110. Buse JB, Klonoff DC, Nielsen LL, et al. Metabolic effects of two years of exenatide treatment on diabetes, obesity, and hepatic biomarkers in patients with type 2 diabetes: an interim analysis of data from the open-label, uncontrolled extension of three double-blind, placebo- controlled trials. Clin Ther. 2007;29(1):139-153. (Pubitemid 46414034)
111. DeFronzo RA, Ratner RE, Han J, Kim DD, Fineman MS, Baron AD, Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes. Diabetes Care. 2005;28(5):1092-1100. (Pubitemid 40616618)
112. Kendall DM, Riddle MC, Rosenstock J, 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):1083-1091. (Pubitemid 40616617)
113. Kim D, MacConell L, Zhuang D, et al. Effects of once-weekly dosing of a long-acting release formulation of exenatide on glucose control and body weight in subjects with type 2 diabetes. Diabetes Care. 2007;30(6):1487-1493. (Pubitemid 46871159)
114. Madsbad S, Schmitz O, Ranstam J, Jakobsen G, Matthews DR; NN2211-1310 International Study Group. Improved glycemic control with no weight increase in patients with type 2 diabetes after once-daily treatment with the long-acting glucagon-like peptide I analog liraglutide (NN2211): a 12-week, double-blind, randomized, controlled trial. Diabetes Care. 2004;27(6):1335-1342. (Pubitemid 38679980)
115. Vilsbøll T, Zdravkovic M, Le-Thi T, et al. Liraglutide, a long-acting human glucagon-like peptide-1 analog, given as monotherapy significantly improves glycemic control and lowers body weight without risk of hypoglycemia in patients with type 2 diabetes. Diabetes Care. 2007;30(6):1608-1610. (Pubitemid 46871185)
116. Gutzwiller JP, Drewe J, Goke B, et al. Glucagon-like peptide-1 promotes satiety and reduces food intake in patients with diabetes mellitus type 2. Am J Physiol. 1999;276(5 pt 2):R1541-R1544. (Pubitemid 29249681)
117. Nielsen LL, Young AA, Parkes DG. Pharmacology of exenatide (synthetic exendin-4): a potential therapeutic for improved glycemic control of type 2 diabetes. Regul Pept. 2004;117(2):77-88. (Pubitemid 38045329)
118. Rayner CK, Samsom M, Jones KL, Horowitz M. Relationships of upper gastrointestinal motor and sensory function with glycemic control. Diabetes Care. 2001;24(2):371-381. (Pubitemid 32119141)
119. Russell-Jones D, Vaag A, Schmitz O, et al. Significantly better glycemic control and weight reduction with liraglutide, a once-daily human GLP-1 analog, compared with insulin glarginc: all as add- on to metformin and a sulfonylurea in type 2 diabetes. Diabetes. 2008;57(suppl 1):A159-A160.
120. Marre M, Shaw J, Brandle M, et al, Liraglutide, a once-daily human GLP-1 analog, added to a sulfonylurea (SU) offers significantly better glycemic control and favorable weight change compared with rosiglitazone and SU combination therapy in subjects with type 2 diabetes. In: 68th Scientific Sessions of the American Diabetes Association (ADA); June 6-10, 2008; San Francisco, CA.
121. Eng J, Kleinman WA, Singh L, Singh G, Raufman JP. Isolation and characterization of exendin-4, an exendin-3 analogue, from Heloderma suspectum venom. Further evidence for an exendin receptor on dispersed acini from guinea pig pancreas. J Biol Chem. 1992;267(11):7402-7405.
122. Drucker DJ. The biology of incretin hormones. Cell Metab. 2006;3(3):153-165. (Pubitemid 43316521)
123. Byetta® [package insert]. San Diego, CA: Amylin Pharmaceuticals, Inc; 2007.
124. Mari A, Nielsen LL, Nanayakkara N, DeFronzo RA, Ferrannini E, Halseth A. Mathematical modeling shows exenatide improved beta-cell function in patients with type 2 diabetes treated with metformin or metformin and a sulfonylurea. Horm Metab Res. 2006;38(12):838-844. (Pubitemid 46051506)
125. Ghofaili KA, Fung M, Ao Z, et al. Effect of exenatide on beta cell function after islet transplantation in type 1 diabetes. Transplantation. 2007;83(1):24-28. (Pubitemid 46104966)
126. Agersø H, Jensen LB, Elbrønd B, Rolan P, Zdravkovic M. The pharmacokinetics, pharmacodynamics, safety and tolerability of NN2211, a new long-acting GLP-1 derivative, in healthy men. Diabetologia. 2002;45(2):195-202. (Pubitemid 34208381)
127. Chang AM, Jakobsen G, Sturis J, et al. The GLP-1 derivative NN2211 restores beta-cell sensitivity to glucose in type 2 diabetic patients after a single dose. Diabetes. 2003;52(7):1786-1791. (Pubitemid 36792471)
128. Nauck MA, Frid A, Hermansen K, et al. Liraglutide, a once-daily human glucagon-like peptide-1 analog, in type 2 diabetes provides similar glycemic control with reduced body weight compared with glimepiride when added to metformin. In: 68th Scientific Sessions of the American Diabetes Association (ADA); June 6 10, 2008; San Francisco, CA.
129. Zinman B, Gerich J, Buse J, et al. Effect of the GLP-1 analogue liraglutide on glycaemic control and weight reduction in patients on metformin and rosiglitazone: a randomised double-blind placebo-controlled trial. In: 44th Annual Meeting of the European Association for the Study of Diabetes (EASD); September 7-11, 2008; Rome, Italy.
130. Blonde L, Rosenstock J, Sesti G, et al. Liraglutide: superior glycemic control vs exenatide when added to metformin and/or SU in type 2 diabetes. In: Canadian Diabetes Association (CDA)/Canadian Society of Endocrinology and Metabolism (CSEM) Professional Conference and Annual Meeting; October 15-18, 2008; Montreal, Quebec, Canada.
131. Brazg R, Xu L, Dalla Man C, Cobelli C, Thomas K, Stein PP. Effect of adding sitagliptin, a dipeptidyl peptidase-4 inhibitor, to metformin on 24-h glycaemic control and beta-cell function in patients with type 2 diabetes. Diabetes Obes Metab. 2007;9(2):186-193. (Pubitemid 46206562)
132. Schweizer A, Couturier A, Foley JE, Dejager S. Comparison between vildagliptin and metformin to sustain reductions in HbA(1c) over 1 year in drug-naive patients with Type 2 diabetes. Diabet Med. 2007;24(9):955-961. (Pubitemid 47301637)
133. Mari A, Scherbaum WA, Nilsson PM, et al. Characterization of the influence of vildagliptin on model-assessed -cell function in patients with type 2 diabetes and mild hyperglycemia, J Clin Endocrinol Metab. 2008;93(1):103-109.
134. Kahn SE. The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of Type 2 diabetes. Diabetologia. 2003;46(1):3-19. (Pubitemid 36237741)
135. Franklin I, Gromada J, Gjinovci A, Theander S, Wollheim CB. Beta-cell secretory products activate alpha-cell ATP-dependent potassium channels to inhibit glucagon release. Diabetes. 2005;54(6):1808-1815. (Pubitemid 40770771)