Abnormalities of Insulin Secretion and β-Cell Defects in Type 2 Diabetes

Textbook of Diabetes: Fourth Edition

Volumn , Issue , 2010, Pages 160-173

  Alsahli, Mazen ^a   Gerich, John E ^a  

^a UNIVERSITY OF ROCHESTER SCHOOL OF MEDICINE AND DENTISTRY   (United States)

Author keywords

Free fatty acid (FFA); Glucose dependent insulinotropic peptide GIP ; Impaired cell function vs insulin resistance; Islet and islet cell changes in type 2 diabetes; Maturity onset diabetes of youth (MODY); Oral glucose tolerance tests (OGTT); Role of cell defects in the natural history of type 2 diabetes; Transcription factor 7 like 2 gene (TCF7L2)

Indexed keywords

EID: 84858300777     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/9781444324808.ch10     Document Type: Chapter

References (165)

1. Wroblewski M, Gottsater A, Lindgarde F, Fernlund P, Sundkvist G. Gender, autoantibodies, and obesity in newly diagnosed diabetic patients aged 40-75 years. Diabetes Care 1998; 21: 250-255.
2. Gerich J. The genetic basis of type 2 diabetes mellitus: impaired insulin secretion versus impaired insulin sensitivity. Endocr Rev 1998; 19: 491-503.
3. Hamman R. Genetic and environmental determinants of noninsulin dependent diabetes mellitus (NIDDM). Diabetes Metab Rev 1992; 8: 287-338.
4. Reaven G. Pathophysiology of insulin resistance in human disease. Physiol Rev 1995; 75: 473-486.
5. DeFronzo R. The triumvirate: B-cell, muscle, and liver: a collusion responsible for NIDDM. Diabetes 1988; 37: 667-687.
6. Olefsky J, Nolan J. Insulin resistance and non-insulin-dependent diabetes mellitus: cellular and molecular mechanisms. Am J Clin Nutr 1995; 61 (Suppl): 980S-986S.
7. Kahn S. The importance of ß-cell failure in the development and progression of type 2 diabetes. J Clin Endocrinol Metab 2001; 86: 4047-4058.
8. Pratley R, Weyer C. The role of impaired early insulin secretion in the pathogenesis of type II diabetes mellitus. Diabetologia 2001; 44: 929-945.
9. Polonsky K, Sturis J, Bell G. Noninsulin-dependent diabetes mellitus: a genetically programmed failure of the beta cell to compensate for insulin resistance. N Engl J Med 1996; 334: 777-783.
10. Himsworth H, Kerr R. Insulin-sensitive and insulin-insensitive types of diabetes mellitus. Clin Sci 1939; 4: 119-152.
11. Yalow R, Berson S. Immunoassay of endogenous plasma insulin in man. J Clin Invest 1960; 3 9: 1157-1175.
12. DeFronzo R, Bonadonna R, Ferrannini E. Pathogenesis of NIDDM: a balanced overview. Diabetes Care 1992; 15: 318-368.
13. Warram J, Martin B, Krolewski A, Soeldener S, Kahn C. Slow glucose removal rate and hyperinsulinemia precede the development of type II diabetes in the offspring of diabetic parents. Ann Intern Med 1990; 113: 909-915.
14. Lillioja S, Mott D, Howard B, Bennet P, Yki-Jarvinen H, Freymond D, et al. Impaired glucose tolerance as a disorder of insulin action: longitudinal and cross-sectional studies in Pima Indians. N Engl J Med 1988; 318: 1217-1225.
15. Seltzer H, Allen E, Herror A, Brennan M. Insulin response to glycemic stimulus: relation of delayed initial release to carbohydrate intolerance in mild diabetes. J Clin Invest 1967; 46: 323-335.
16. Mitrakou A, Kelley D, Mokan M, Veneman T, Pangburn T, Reilly J, et al. Role of reduced suppression of glucose production and diminished early insulin release in impaired glucose tolerance. N Engl J Med 1992; 326: 22-29.
17. Calles-Escandon J, Robbins, D. Loss of early phase of insulin release in humans impairs glucose tolerance and blunts thermic effect of glucose. Diabetes 1987; 36: 1167-1172.
18. Luzi L, DeFronzo R. Effect of loss of first-phase insulin secretion on hepatic glucose production and tissue glucose disposal in humans. Am J Physiol 1989; 257: E241-E246.
19. Hollander P, Schwartz S, Gatlin M, Haas S, Zheng H, Foley J, et al. Importance of early insulin secretion: comparison of nateglinide and glyburide in previously diet-treated patients with type 2 diabetes. Diabetes Care 2001; 24: 983-988.
20. Perley J, Kipnis D. Plasma insulin responses to oral and intravenous glucose: studies in normal and diabetic subjects. J Clin Invest 1967; 46: 1954-1962.
21. Stumvoll M, Mitrakou A, Pimenta W, Jenssen T, Yki-Järvinen H, Van Haeften T, et al. Use of the oral glucose tolerance test to assess insulin release and insulin sensitivity. Diabetes Care 2000; 23: 295-301.
22. Weyer C, Bogardus C, Mott D, Pratley R. The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus. J Clin Invest 1999; 104: 787-794.
23. Karam J, Grodsky G, Ching K, Schmid F, Burrill K, Forsham P. "Staircase" glucose stimulation of insulin secretion in obesity: measure of beta-cell sensitivity and capacity. Diabetes 1974; 23: 763-770.
24. Bergman R, Phillips J, Cobelli C. Physiologic evaluation of factors controlling glucose tolerance in man: measurement of insulin sensitivity and B-cell glucose sensitivity from the response to intravenous glucose. J Clin Invest 1981; 68: 1456-1467.
25. Buchanan T. Pancreatic B-cell defects in gestational diabetes: implications for the pathogenesis and prevention of type 2 diabetes. J Clin Endocrinol Metab 2001; 86: 989-993.
26. Borch-Johnson K, Nissen H, Hendriksen E, Kreiner S, Salling N, Deckert T, et al. The natural history of insulin-dependent diabetes mellitus in Denmark: long term survival with and without diabetic complications. Diabet Med 1987; 4: 201-210.
27. Vaag A, Henriksen J, Madsbad S, Holm N. Insulin secretion, insulin action, and hepatic glucose production in identical twins discordant for non-insulin-dependent diabetes mellitus. J Clin Invest 1995; 95: 690-698.
28. Johnston C, Ward K, Beard C, McKnight B, Porte D. Islet function and insulin sensitivity in the nondiabetic offspring of conjugal type II diabetic patients. Diabetic Med 1990; 7: 119-125.
29. Pimenta W, Kortytkowski M, Mitrakou A, Jenssen T, Yki-Jarvinen H, Evron W, et al. Pancreatic beta-cell dysfunction as the primary genetic lesion in NIDDM: evidence from studies in normal glucose-tolerant individuals with a first-degree NIDDM relative. JAMA 1995; 273: 1855-1861.
30. Ferrannini E, Gastaldelli A, Miyazaki Y, Matsuda M, Mari A, DeFronzo RA. Beta-cell function in subjects spanning the range from normal glucose tolerance to overt diabetes: a new analysis. J Clin Endocrinol Metab 2005; 90: 493-500.
31. Vaag A, Alford F, Beck-Nielsen H. Intracellular glucose and fat metabolism in identical twins discordant for non-insulin-dependent diabetes mellitus (NIDDM): acquired versus genetic metabolic defects. Diabetic Med 1996; 13: 806-815.
32. Chiu KC, Lee NP, Cohan P, Chuang LM. Beta cell function declines with age in glucose tolerant Caucasians. Clin Endocrinol (Oxf) 2000; 53: 569-575.
33. Szoke E, Shrayyef MZ, Messing S, Woerle HJ, van Haeften TW, Meyer C, et al. Effect of aging on glucose homeostasis: accelerated deterioration of beta-cell function in individuals with impaired glucose tolerance. Diabetes Care 2008; 31: 539-543.
34. Iozzo P, Beck-Nielsen H, Laakso M, Smith U, Yki-Jarvinen H, Ferrannini E. Independent influence of age on basal insulin secretion in nondiabetic humans. European Group for the Study of Insulin Resistance. J Clin Endocrinol Metab 1999; 84: 863-868.
35. Fritsche A, Madaus A, Stefan N, Tschritter O, Maerker E, Teigeler A, et al. Relationships among age, proinsulin conversion, and beta-cell function in nondiabetic humans. Diabetes 2002; 51 (Suppl 1): S234-S239.
36. Utzschneider KM, Carr DB, Hull RL, Kodama K, Shofer JB, Retzlaff BM, et al. Impact of intra-abdominal fat and age on insulin sensitivity and beta-cell function. Diabetes 2004; 53: 2867-2872.
37. UK Prospective Diabetes Study Group. UK Prospective Diabetes study 16. Overview of 6 years'therapy of type II diabetes: a progressive disease. Diabetes 1995; 44: 1249-1258.
38. Kahn SE, Haffner SM, Heise MA, Herman WH, Holman RR, Jones NP, et al. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med 2006; 355: 2427-2443.
39. Kahn SE, Halban PA. Release of incompletely processed proinsulin is the cause of the disproportionate proinsulinemia of NIDDM. Diabetes 1997; 46: 1725-1732.
40. Ward WK, LaCava EC, Paquette TL, Beard JC, Wallum BJ, Porte D Jr. Disproportionate elevation of immunoreactive proinsulin in type 2 (non-insulin-dependent) diabetes mellitus and in experimental insulin resistance. Diabetologia 1987; 30: 698-702.
41. Matthews D. Physiological implications of pulsatile hormone secretion. Ann N Y Acad Sci 1991; 618: 28-37.
42. Porksen N, Hollingdal M, Juhl C, Butler P, Veldhuis JD, Schmitz O. Pulsatile insulin secretion: detection, regulation, and role in diabetes. Diabetes 2002; 51 (Suppl 1): S245-S254.
43. Porksen N, Nyholm B, Veldhuis JD, Butler PC, Schmitz O. In humans at least 75% of insulin secretion arises from punctuated insulin secretory bursts. Am J Physiol 1997; 273: E908-E914.
44. Porksen N, Munn S, Steers J, Vore S, Veldhuis J, Butler P. Pulsatile insulin secretion accounts for 70% of total insulin secretion during fasting. Am J Physiol 1995; 269: E478-E488.
45. Porksen N, Grofte B, Nyholm B, Holst JJ, Pincus SM, Veldhuis JD, et al. Glucagon-like peptide 1 increases mass but not frequency or orderliness of pulsatile insulin secretion. Diabetes 1998; 47: 45-49.
46. Porksen NK, Munn SR, Steers JL, Schmitz O, Veldhuis JD, Butler PC. Mechanisms of sulfonylurea's stimulation of insulin secretion in vivo: selective amplification of insulin secretory burst mass. Diabetes 1996; 45: 1792-1797.
47. Porksen N, Munn S, Steers J, Veldhuis JD, Butler PC. Effects of glucose ingestion versus infusion on pulsatile insulin secretion: the incretin effect is achieved by amplification of insulin secretory burst mass. Diabetes 1996; 45: 1317-1323.
48. Ritzel R, Schulte M, Porksen N, Nauck MS, Holst JJ, Juhl C, et al. Glucagon-like peptide 1 increases secretory burst mass of pulsatile insulin secretion in patients with type 2 diabetes and impaired glucose tolerance. Diabetes 2001; 50: 776-784.
49. Porksen N, Munn SR, Steers JL, Veldhuis JD, Butler PC. Effects of somatostatin on pulsatile insulin secretion: elective inhibition of insulin burst mass. Am J Physiol 1996; 270: E1043-E1049.
50. Porksen N, Hussain MA, Bianda TL, Nyholm B, Christiansen JS, Butler PC, et al. IGF-1 inhibits burst mass of pulsatile insulin secretion at supraphysiological and low IGF-1 infusion rates. Am J Physiol 1997; 272: E352-E358.
51. 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: 442-448.
52. Sturis J, Van Cauter E, Blackman JD, Polonsky KS. Entrainment of pulsatile insulin secretion by oscillatory glucose infusion. J Clin Invest 1991; 87: 439-445.
53. Ferner RE, Ashworth L, Tronier B, Alberti KG. Effects of short-term hyperglycemia on insulin secretion in normal humans. Am J Physiol 1986; 250: E655-E661.
54. VanHaeften T, Voetberg G, Gerich J, Van der Veen E. Dose-response characteristics for arginine-stimulated insulin secretion in man and influence of hyperglycemia. J Clin Endocrinol Metab 1989; 69: 1059-1064.
55. VanHaeften T, VAn Maarschalkerveerd W, Gerich J, Van der Veen E. Decreased insulin secretory capacity and normal pancreatic B-cell glucose sensitivity in non-obese patients with NIDDM. Eur J Clin Invest 1991; 21: 168-174.
56. Dimitriadis G, Pehling G, Gerich J. Abnormal glucose modulation of islet A-and B-cell responses to arginine in non-insulin-dependent diabetes mellitus. Diabetes 1985; 34: 541-547.
57. Hollander P, Asplin C, Palmer J. Glucose modulation of insulin and glucagon secretion in nondiabetic and diabetic man. Diabetes 1982; 31: 489-495.
58. Ward W, Bolgiano D, McKnight B, Halter J, Porte D. Diminished ß-cell secretory capacity in patients with noninsulin-dependent diabetes mellitus. J Clin Invest 1984; 74: 1318-1328.
59. Sturis J, Polonsky KS, Shapiro ET, Blackman JD, O'Meara NM, Van Cauter E. Abnormalities in the ultradian oscillations of insulin secretion and glucose levels in type 2 (non-insulin-dependent) diabetic patients. Diabetologia 1992; 35: 681-689.
60. Yoshioka N, Kuzuya T, Matsuda A, Taniguchi M, Iwamoto Y. Serum proinsulin levels at fasting and after oral glucose load in patients with type 2 (non-insulin-dependent) diabetes mellitus. Diabetologia 1988; 31: 355-360.
61. Van Haeften T, Pimenta W, Mitrakou A, Korytkowski M, Jenssen T, Yki-Järvinen H, et al. Relative contributions of ß-cell function and tissue insulin sensitivity to fasting and postglucose-load glycemia. Metabolism 2000; 49: 1318-1325.
62. Larsson H, Berglund G, Ahren B. Glucose modulation of insulin and glucagon secretion is altered in impaired glucose tolerance. J Clin Endocrinol Metab 1995; 80: 1778-1782.
63. O'Meara N, Sturis J, VanCouter E, Polonsky K. Lack of control by glucose of ultradian insulin secretory oscillations in impaired glucose tolerance and in non-insulin-dependent diabetes mellitus. J Clin Invest 1993; 92: 262-271.
64. O'Rahilly S, Turner R, Matthews D. Impaired pulsatile secretion of insulin in relatives of patients with noninsulin-dependent diabetes. N Engl J Med 1988; 318: 1225-1230.
65. Larsson H, Ahren B. Relative hyperproinsulinemia as a sign of islet dysfunction in women with impaired glucose tolerance. J Clin Endocrinol Metab 1999; 84: 2068-2074.
66. Cerasi E, Luft R. Insulin response to glucose infusion in diabetic and nondiabetic monozygotic twin pairs: genetic control of insulin response. Acta Endocrinol 1967; 55: 330-345.
67. Barnett A, Spiliopoulos A, Pyke D, Stubbs W, Burrin J, Alberti K. Metabolic studies in unaffected co-twins of noninsulin dependent diabetics. Br Med J 1981; 282: 1656-1658.
68. Pyke D, Taylor K. Glucose tolerance and serum insulin in unaffected identical twins of diabetics. Br Med J 1967; 4: 21-22.
69. Polonsky K, Given B, Hirsch L, Shapiro E, Tillil H, Beebe C, et al. Quantitative study of insulin secretion and clearance in normal and obese subjects. J Clin Invest 1988; 81: 435-441.
70. Bell G, Polonsky K. Diabetes mellitus and genetically programmed defects in ß-cell function. Nature 2001; 414: 788-791.
71. Busch C, Hegele R. Genetic determinants of type 2 diabetes mellitus. Clin Genet 2001; 60: 243-254.
72. Edlund H. Factors controlling pancreatic cell differentiation and function. Diabetologia 2001; 44: 1071-1079.
73. Stumvoll M, Goldstein BJ, van Haeften TW. Pathogenesis of type 2 diabetes. Endocr Res 2007; 32: 19-37.
74. Stefan N, Fritsche A, Haring H, Stumvoll M. Effect of experimental elevation of free fatty acids on insulin secretion and insulin sensitiv ity in healthy carriers of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor-gamma2 gene. Diabetes 2001; 50: 1143-1148.
75. Horikawa Y, Oda N, Cox N, Li X, Orho-Melander M, Hara M, et al. Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus. Nat Genet 2000; 26: 163-175.
76. Gloyn AL, Weedon MN, Owen KR, Turner MJ, Knight BA, Hitman G, et al. Large-scale association studies of variants in genes encoding the pancreatic beta-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) confirm that the KCNJ11 E23K variant is associated with type 2 diabetes. Diabetes 2003; 52: 568-572.
77. Florez JC, Jablonski KA, Kahn SE, Franks PW, Dabelea D, Hamman RF, et al. Type 2 diabetes-associated missense polymorphisms KCNJ11 E23K and ABCC8 A1369S influence progression to diabetes and response to interventions in the Diabetes Prevention Program. Diabetes 2007; 56: 531-536.
78. Florez JC, Jablonski KA, Bayley N, Pollin TI, de Bakker PI, Shuldiner AR, et al. TCF7L2 polymorphisms and progression to diabetes in the Diabetes Prevention Program. N Engl J Med 2006; 355: 241-250.
79. Zhang C, Qi L, Hunter DJ, Meigs JB, Manson JE, van Dam RM, Hu FB. Variant of transcription factor 7-like 2 (TCF7L2) gene and the risk of type 2 diabetes in large cohorts of US women and men. Diabetes 2006; 55: 2645-2648.
80. Grant SF, Thorleifsson G, Reynisdottir I, Benediktsson R, Manolescu A, Sainz J, et al. Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nat Genet 2006; 38: 320-323.
81. Yi F, Brubaker PL, Jin T. TCF-4 mediates cell type-specific regulation of proglucagon gene expression by beta-catenin and glycogen synthase kinase-3beta. J Biol Chem 2005; 280: 1457-1464.
82. Saltiel A, Kahn C. Insulin signalling and the regulation of glucose and lipid metabolism. Nature 2001; 414: 799-806.
83. Hales C, Barker D, Clark P, Cox L, Fall C, Osmond C, et al. Fetal and infant growth and impaired glucose tolerance at age 64. Br Med J 1991; 303: 1019-1022.
84. Hales C, Barker D. Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Diabetologia 1992; 35: 595-601.
85. Weyer C, Pratley R, Tataranni PA. Role of insulin resistance and insulin secretory dysfunction in the pathogenesis of type 2 diabetes mellitus: lessons from cross-sectional, prospective, and longitudinal studies in Pima Indians. Curr Opin Endocrinol Diabetes Obes 2002; 9: 130-138.
86. Yki-Järvinen H. Glucose toxicity. Endocr Rev 1992; 13: 415-431.
87. Meyer J, Sturis J, Katschinski M, Arnold R, Goke B, Byrne M. Acute hyperglycemia alters the ability of the normal beta-cell to sense and respond to glucose. Am J Physiol Endocrinol Metab 2002; 282: E917-E922.
88. Kosaka K, Kuzuya T, Hagura R. Increase in insulin response after treatment of overt maturity-onset diabetes is independent of the mode of treatment. Diabetologia 1980; 18: 23-28.
89. Garvey W, Olefsky J, Griffin J, Hamman R, Kolterman O. The effect of insulin treatment on insulin secretion and insulin action in type II diabetes mellitus. Diabetes 1985; 34: 222-234.
90. Andrews W, Vasquez B, Nagulesparan M, Klimes I, Foley J, Unger R, et al. Insulin therapy in obese non-insulin-dependent diabetes induces improvements in insulin action and secretion that are maintained for two weeks after insulin withdrawal. Diabetes, 1984; 33: 634-642.
91. Yki-Jarvinen H. Thiazolidinediones. N Engl J Med 2004; 351: 1106-1118.
92. Poitout V, Robertson RP. Glucolipotoxicity: fuel excess and beta-cell dysfunction. Endocr Rev 2008; 29: 351-366.
93. Perriello G, Mitrakou A, Gumbiner B, Gerich J. Non-esterified fatty acids in non-insulin-dependent diabetes: a critical update. Diabetes Ann 1995; 91-106.
94. Jansson PA, Larrson A, Smith V, Lonroth P. Glycerol production in subcutaneous adipose tissue in lean and obese humans. J Clin Invest 1992; 89: 1610-1617.
95. Taskinen M, Bogardus C, Kennedy A, Howard B. Multiple disturbances of free fatty acid metabolism in noninsulin dependent diabetes. J Clin Invest 1985; 76: 637-644.
96. Poitout V, Robertson R. Minireview: Secondary beta-cell failure in type 2 diabetes: a convergence of glucotoxicity and lipotoxicity. Endocrinology 2002; 143: 339-342.
97. Poitout V. Lipid partitioning in the pancreatic ß-cell: physiologic and pathophysiologic implications. Curr Opin Endocrinol Diabetes Obes 2002; 9: 152-159.
98. Fleury C, Sanchis D. The mitochondrial uncoupling protein-2: current status. Int J Biochem Cell Biol 1999; 31: 1261-1278.
99. Chan CB, MacDonald PE, Saleh MC, Johns DC, Marban E, Wheeler MB. Overexpression of uncoupling protein 2 inhibits glucose-stimulated insulin secretion from rat islets. Diabetes 1999; 48: 1482-1486.
100. Medvedev AV, Robidoux J, Bai X, Cao W, Floering LM, Daniel KW, et al. Regulation of the uncoupling protein-2 gene in INS-1 beta-cells by oleic acid. J Biol Chem 2002; 277: 42639-42644.
101. Hagman DK, Hays LB, Parazzoli SD, Poitout V. Palmitate inhibits insulin gene expression by altering PDX-1 nuclear localization and reducing MafA expression in isolated rat islets of Langerhans. J Biol Chem 2005; 280: 32413-32418.
102. Carpentier A, Mittelman SD, Bergman RN, Giacca A, Lewis GF. Prolonged elevation of plasma free fatty acids impairs pancreatic beta-cell function in obese nondiabetic humans but not in individuals with type 2 diabetes. Diabetes 2000; 49: 399-408.
103. Boden G. Role of fatty acids in the pathogenesis of insulin resistance and NIDDM. Diabetes 1997; 46: 3-10.
104. Choi B, Shi F. Risk factors for diabetes mellitus by age and sex: results of the national population health survey. Diabetologia 2001; 44: 1221-1231.
105. Hotamisligil G, Spiegelman B. Tumor necrosis factor a: a key component of the obesity-diabetes link. Diabetes 1994; 43: 1271-1278.
106. Steppan C, Bailey S, Bhat S, Brown E, Banerjee R, Wright C, et al. The hormone resistin links obesity to diabetes. Nature 2001; 409: 307-312.
107. Ahima R, Flier J. Leptin. Annu Rev Physiol 2000; 62: 413-437.
108. Ahima R, Flier J. Adipose tissue as an endocrine organ. Trends Endocrinol Metab 2000; 11: 327-332.
109. Sanke T, Hanabusa T, Nakano Y, Oki C, Okai K, Nishimura S, et al. Plasma islet amyloid polypeptide (amylin) levels and their responses to oral glucose in type 2 (non-insulin-dependent) diabetic patients. Diabetologia 1991; 34: 129-132.
110. Kelley D, Goodposter B. Skeletal muscle triglyceride: an aspect of regional adiposity and insulin resistance. Diabetes Care 2001; 24: 933-941.
111. Virkamaki A, Korsheninnikova E, Seppala-Lindroos A, Vehkavaara S, Goto T, Halavaara J, et al. Intramyocellular lipid is associated with resistance to in vivo insulin actions on glucose uptake, antilipolysis,and early insulin signaling pathways in human skeletal muscle. Diabetes 2001; 50: 2337-2343.
112. Creutzfeldt W, Nauck M. Gut hormones and diabetes mellitus. Diabetes Metab Rev 1992; 8: 149-177.
113. 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: 2270-2276.
114. 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: 367-379.
115. Wang Q, Brubaker PL. Glucagon-like peptide-1 treatment delays the onset of diabetes in 8 week-old db/db mice. Diabetologia 2002; 45: 1263-1273.
116. Trumper A, Trumper K, Trusheim H, Arnold R, Goke B, Horsch D. Glucose-dependent insulinotropic polypeptide is a growth factor for beta (INS-1) cells by pleiotropic signaling. Mol Endocrinol 2001; 15: 1559-1570.
117. Krarup T. Immunoreactive gastric inhibitory polypeptide. Endocr Rev 1988; 9: 122-134.
118. 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: 415-423.
119. Vilsboll T, Krarup T, Sonne J, Madsbad S, Volund A, Juul AG, et al. Incretin secretion in relation to meal size and body weight in healthy subjects and people with type 1 and type 2 diabetes mellitus. J Clin Endocrinol Metab 2003; 88: 2706-2713.
120. O'Donovan DG, Doran S, Feinle-Bisset C, Jones KL, Meyer JH, Wishart JM, et al. Effect of variations in small intestinal glucose delivery on plasma glucose, insulin, and incretin hormones in healthy subjects and type 2 diabetes. J Clin Endocrinol Metab 2004; 89: 3431-3435.
121. Knop FK, Vilsboll T, Hojberg PV, Larsen S, Madsbad S, Volund A, et al. Reduced incretin effect in type 2 diabetes: cause or consequence of the diabetic state? Diabetes 2007; 56: 1951-1959.
122. Nauck M, Stockmann F, Ebert R, Creutzfeldt W. Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia 1986; 29: 46-52.
123. 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: 380-386.
124. 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: 1111-1119.
125. Nauck MA, El Ouaghlidi A, Gabrys B, Hucking K, Holst JJ, Deacon CF, et al. Secretion of incretin hormones (GIP and GLP-1) and incretin effect after oral glucose in first-degree relatives of patients with type 2 diabetes. Regul Pept 2004; 122: 209-217.
126. Amori RE, Lau J, Pittas AG. Efficacy and safety of incretin therapy in type 2 diabetes: systematic review and meta-analysis. JAMA 2007; 298: 194-206.
127. 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: 8628-8632.
128. Westermark P, Wernstedt C, O'Brien TD, Hayden DW, Johnson KH. Islet amyloid in type 2 human diabetes mellitus and adult dia-betic cats contains a novel putative polypeptide hormone. Am J Pathol 1987; 127: 414-417.
129. Cooper G. Amylin compared with calcitonin gene-related peptide: structure, biology, and relevance to metabolic disease. Endocr Rev 1994; 15: 163-201.
130. Lorenzo A, Razzaboni B, Weir G, Yankner B. Pancreatic islet cell toxicity of amylin associated with type-2 diabetes mellitus. Nature 1994; 368: 756-760.
131. Clark A, Wells C, Buley I, Cruickshank J, Vanhegan R, Matthews D, et al. Islet amyloid, increased alpha-cells, reduced beta-cells and exocrine fibrosis: quantitative changes in the pancreas in type 2 diabetes. Diabetes Res 1988; 9: 151-159.
132. Haataja L, Gurlo T, Huang CJ, Butler PC. Islet amyloid in type 2 diabetes, and the toxic oligomer hypothesis. Endocr Rev 2008; 29: 303-316.
133. Meier JJ, Kayed R, Lin CY, Gurlo T, Haataja L, Jayasinghe S, et al. Inhibition of human IAPP fibril formation does not prevent beta-cell death: evidence for distinct actions of oligomers and fibrils of human IAPP. Am J Physiol Endocrinol Metab 2006; 291: E1317-E1324.
134. Seino S. S20G mutation of the amylin gene is associated with type II diabetes in Japanese. Study Group of Comprehensive Analysis of Genetic Factors in Diabetes Mellitus. Diabetologia 2001; 44: 906-909.
135. Ma Z, Westermark GT, Sakagashira S, Sanke T, Gustavsson A, Sakamoto H, et al. Enhanced in vitro production of amyloid-like fibrils from mutant (S20G) islet amyloid polypeptide. Amyloid 2001; 8: 242-249.
136. Eizirik DL, Cardozo AK, Cnop M. The role for endoplasmic reticulum stress in diabetes mellitus. Endocr Rev 2008; 29: 42-61.
137. Loweth AC, Williams GT, James RF, Scarpello JH, Morgan NG. Human islets of Langerhans express Fas ligand and undergo apoptosis in response to interleukin-1 ß and Fas ligation. Diabetes 1998; 47: 727-732.
138. Mandrup-Poulsen T. The role of interleukin-1 in the pathogenesis of IDDM. Diabetologia 1996; 39: 1005-1029.
139. Maedler K, Sergeev P, Ehses JA, Mathe Z, Bosco D, Berney T, et al. Leptin modulates beta cell expression of IL-1 receptor antagonist and release of IL-1beta in human islets. Proc Natl Acad Sci U S A 2004; 101: 8138-8143.
140. Maedler K, Sergeev P, Ris F, Oberholzer J, Joller-Jemelka HI, Spinas GA, et al. Glucose-induced beta cell production of IL-1beta contributes to glucotoxicity in human pancreatic islets. J Clin Invest 2002; 110: 851-860.
141. Maedler K, Schumann DM, Sauter N, Ellingsgaard H, Bosco D, Baertschiger R, et al. Low concentration of interleukin-1beta induces FLICE-inhibitory protein-mediated beta-cell proliferation in human pancreatic islets. Diabetes 2006; 55: 2713-2722.
142. Donath MY, Storling J, Berchtold LA, Billestrup N, Mandrup-Poulsen T. Cytokines and beta-cell biology: from concept to clinical translation. Endocr Rev 2008; 29: 334-350.
143. Maedler K, Spinas GA, Lehmann R, Sergeev P, Weber M, Fontana A, et al. Glucose induces beta-cell apoptosis via upregulation of the Fas receptor in human islets. Diabetes 2001; 50: 1683-1690.
144. Larsen CM, Faulenbach M, Vaag A, Volund A, Ehses JA, Seifert B, et al. Interleukin-1-receptor antagonist in type 2 diabetes mellitus. N Engl J Med 2007; 356: 1517-1526.
145. Kolb H, Mandrup-Poulsen T. An immune origin of type 2 diabetes? Diabetologia 2005; 48: 1038-1050.
146. Kahn SE, D'Alessio DA, Schwartz MW, Fujimoto WY, Ensinck JW, Taborsky GJ Jr, et al. Evidence of cosecretion of islet amyloid polypeptide and insulin by beta-cells. Diabetes 1990; 39: 634-638.
147. Hull RL, Westermark GT, Westermark P, Kahn SE. Islet amyloid: a critical entity in the pathogenesis of type 2 diabetes. J Clin Endocrinol Metab 2004; 89: 3629-3643.
148. Hoppener JW, Ahren B, Lips CJ. Islet amyloid and type 2 diabetes mellitus. N Engl J Med 2000; 343: 411-419.
149. Saito K, Iwama N, Takahashi T. Morphometrical analysis on topographical difference in size distribution, number and volume of islets in the human pancreas. Tohoku J Exp Med 1978; 124: 177-186.
150. Sakuraba H, Mizukami H, Yagihashi N, Wada R, Hanyu C, Yagihashi S. Reduced beta-cell mass and expression of oxidative stress-related DNA damage in the islet of Japanese type II diabetic patients. Diabetologia 2002; 45: 85-96.
151. Rahier J, Goebbels R, Henquin J. Cellular composition of the human diabetic pancreas. Diabetologia 1983; 24: 366-371.
152. Del Guerra S, Lupi R, Marselli L, Masini M, Bugliani M, Sbrana S, et al. Functional and molecular defects of pancreatic islets in human type 2 diabetes. Diabetes 2005; 54: 727-735.
153. Kloppel G, Lohr M, Habich K, Oberholzer M, Heitz P. Islet pathology and the pathogenesis of type 1 and type 2 diabetes mellitus revisited ed. S urv Synth Pathol Res 1985; 4: 110-125.
154. 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: 102-110.
155. Stefan Y, Orci L, Malaisse-Lagae F, Perrelet A, Patel Y, Unger RH. Quantitation of endocrine cell content in the pancreas of nondiabetic and diabetic humans. Diabetes 1982; 31: 694-700.
156. Gepts W. [Contribution to the morphological study of the islands of Langerhans in diabetes; study of the quantitative variations of the different insular constituents.] Ann Soc R Sci Med Nat Brux 1957; 10: 5-108.
157. Saito K, Yaginuma N, Takahashi T. Differential volumetry of A, B, and D cells in the pancreatic islets of diabetic and nondiabetic subjects. Tohoku J Exp Med 1979; 129: 273-283.
158. Westermark P, Wilander E. The influence of amyloid deposits on the islet volume in maturity onset diabetes mellitus. Diabetologia 1978; 15: 417-421.
159. Rahier J, Guiot Y, Goebbels RM, Sempoux C, Henquin JC. Pancreatic beta-cell mass in European subjects with type 2 diabetes. Diabetes Obes Metab 2008; 10 (Suppl 4): 32-42.
160. Marchetti P, Del Guerra S, Marselli L, Lupi R, Masini M, Pollera M, et al. Pancreatic islets from type 2 diabetic patients have functional defects and increased apoptosis that are ameliorated by metformin. J Clin Endocrinol Metab 2004; 89: 5535-5541.
161. 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: 253-283.
162. Iki K, Pour PM. Distribution of pancreatic endocrine cells including IAPP-expressing cells in non-diabetic and type 2 diabetic cases. J Histochem Cytochem 2007; 55: 111-118.
163. Gerich J. Somatostatin and diabetes. Am J Med 1981; 70: 619-626.
164. Basabe J, Karabatas L, Arata M, Pivetta O, Cresto J. Secretion and effect of somatostatin in early stages of the diabetic syndrome in C57BL/KsJ-mdb mice. Diabetologia 1986; 29: 485-488.
165. Polonsky KS, Given BD, Hirsch LJ, Tillil H, Shapiro ET, Beebe C, et al. Abnormal patterns of insulin secretion in non-insulin-dependent diabetes mellitus. N Engl J Med 1988; 318: 1231-1239.