References

1. Hogan P, Dall T, Nikolov P. American Diabetes Association. Economic costs of diabetes in the US in 2002. Diabetes Care 2003;26:917-932.

2. Knowler WC, Barrett-Connor E, Fowler SE, et al. Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346:393-403.

3. Zimmet P, Lefebvre P. The global NIDDM epidemic. Treating the disease and ignoring the symptom. Diabetologia 1996;39: 1247-1248.

4. Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 2004;27:1047-1053.

5. Hedley AA, Ogden CL, Johnson CL, Carroll MD, Curtin LR, Flegal KM. Prevalence of overweight and obesity among US children, adolescents and adults, 1999-2002. JAMA 2004;291:2847-2850.

6. Schulze MB, Manson JE, Ludwig DS, et al. Sugar-sweetened beverages, weight gain, and incidence of type 2 diabetes in young and middle-aged women. JAMA 2004;292:927-934.

7. Caroli M, Argentieri L, Cardone M, Masi A. Role of television in childhood obesity prevention. Int J Obes Relat Metab Disord 2004;28 (Suppl 3):S104-S108.

8. DeFronzo RA. Pathogenesis of type 2 diabetes mellitus. Med Clin North Am 2004;88:787-835.

9. Barnett AH, Eff C, Leslie RD, Pyke DA. Diabetes in identical twins. A study of 200 pairs. Diabetologia 1981;20:87-93.

10. van den Ouweland JM, Lemkes HH, Trembath RC, et al. Maternally inherited diabetes and deafness is a distinct subtype of diabetes and associates with a single point mutation in the mitochondrial tRNA(Leu(UUR)) gene. Diabetes. 1994;43:746-751.

11. Inoue H, Tanizawa Y, Wasson J, et al. A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome). Nat Genet 1998;20:143-148.

12. Porter JR, Barrett TG. Monogenic syndromes of abnormal glucose homeostasis: clinical review and relevance to the understanding of the pathology of insulin resistance and beta cell failure. J Med Genet 2005;42:893-902.

13. Bell GI, Polonsky KS. Diabetes mellitus and genetically programmed defects in beta-cell function. Nature 2001;414:788-791.

14. Hanis CL, Boerwinkle E, Chakraborty R, et al. A genome-wide search for human non-insulin-dependent (type 2) diabetes genes reveals a major susceptibility locus on chromosome 2. Nat Genet 1996;13:161-166.

15. Horikawa Y, Oda N, Cox NJ, et al. Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus. Nat Genet 2000;26:163-175.

16. Marshall C, Hitman GA, Partridge CJ, et al. Evidence that an isoform of calpain-10 is a regulator of exocytosis in pancreatic beta-cells. Mol Endocrinol 2005;19:213-224.

17. Gunton JE, Kulkarni RN, Yim S, et al. Loss of ARNT/HIF1beta mediates altered gene expression and pancreatic-islet dysfunction in human type 2 diabetes. Cell. 2005;122:337-349.

18. Porzio O, Federici M, Hribal ML, et al. The Gly972-->Arg amino acid polymorphism in IRS-1 impairs insulin secretion in pancreatic beta cells. J Clin Invest 1999;104:357-364.

19. Florez JC, Sjogren M, Burtt N, et al. Association testing in 9,000 people fails to confirm the association of the insulin receptor substrate-1 G972R polymorphism with type 2 diabetes. Diabetes 2004;53:3313-3318.

20. Grant SF, Thorleifsson G, Reynisdottir I, et al. Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nat Genet 2006;38:320-323.

21. Neve B, Fernandez-Zapico ME, Ashkenazi-Katalan V, et al. Role of transcription factor KLF11 and its diabetes-associated gene variants in pancreatic beta cell function. Proc Natl Acad Sci USA 2005;102:4807-4812.

22. Gloyn AL, Weedon MN, Owen KR, 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.

23. van Dam RM, Hoebee B, Seidell JC, Schaap MM, de Bruin TW, Feskens EJ. Common variants in the ATP-sensitive K+ channel genes KCNJ11 (Kir6.2) and ABCC8 (SUR1) in relation to glucose intolerance: population-based studies and meta-analyses. Diabet Med 2005;22:590-598.

24. Hu FB, Manson JE, Stampfer MJ, et al. Diet, lifestyle, and the risk of type 2 diabetes mellitus in women. N Engl J Med 2001;345: 790-797.

25. Koppes LL, Dekker JM, Hendriks HF, Bouter LM, Heine RJ. Moderate alcohol consumption lowers the risk of type 2 diabetes: a meta-analysis of prospective observational studies. Diabetes Care 2005;28:719-725.

26. Mallon L, Broman JE, Hetta J. High incidence of diabetes in men with sleep complaints or short sleep duration: a 12-year follow-up study of a middle-aged population. Diabetes Care 2005;28:2762-2767.

27. van Dam RM, Hu FB. Coffee consumption and risk of type 2 diabetes: a systematic review. JAMA 2005;294:97-104.

28. O'Dea K. Marked improvement in carbohydrate and lipid metabolism in diabetic Australian aborigines after temporary reversion to traditional lifestyle. Diabetes 1984;33:596-603.

29. Weiss R, Dziura J, Burgert TS, et al. Obesity and the metabolic syndrome in children and adolescents. N Engl J Med 2004;350: 2362-2374.

30. Dabelea D, Snell-Bergeon JK, Hartsfield CL, Bischoff KJ, Hamman RF, McDuffie RS; Kaiser Permanente of Colorado GDM Screening Program. Increasing prevalence of gestational diabetes mellitus (GDM) over time and by birth cohort: Kaiser Permanente of Colorado GDM Screening Program. Diabetes Care 2005;28:579-584.

31. Pan XR, Li GW, Hu YH, et al. Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. The Da Qing IGT and Diabetes Study. Diabetes Care 1997;20:537-544.

32. Tuomilehto J, Lindstrom J, Eriksson JG, et al; Finnish Diabetes Prevention Study Group. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 2001;344:1343-1350.

33. Turner RC, McCarthy ST, Holman RR, Harris E. Beta-cell function improved by supplementing basal insulin secretion in mild diabetes. Br Med J 1976;1:1252-1254.

34. Kosaka K, Kuzuya T, Akanuma Y, 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.

35. Li Y, Xu W, Liao Z, et al. Induction of long-term glycemic control in newly diagnosed type 2 diabetic patients is associated with improvement of beta-cell function. Diabetes Care 2004;27:2597-2602.

36. Peters AL, Davidson MB. Maximal dose glyburide therapy in markedly symptomatic patients with type 2 diabetes: a new use for an old friend. J Clin Endocrinol Metab 1996;81:2423-2427.

37. Garvey WT, Olefsky JM, Griffin J, Hamman RF, Kolterman OG. The effect of insulin treatment on insulin secretion and insulin action in type II diabetes mellitus. Diabetes 1985;34:222-234.

38. Rossetti L, Giaccari A, DeFronzo RA. Glucose toxicity. Diabetes Care 1990;13:610-630.

39. Leahy JL, Bonner-Weir S, Weir GC. Beta-cell dysfunction induced by chronic hyperglycemia. Current ideas on the mechanism of the impaired glucose-induced insulin secretion. Diabetes Care 1992;15:442-455.

40. Leahy JL, Cooper HE, Deal DA, Weir GC. Chronic hyperglycemia is associated with impaired glucose influence on insulin secretion. A study in normal rats using chronic in vivo glucose infusions. J Clin Invest 1986;77:908-915.

41. Rossetti L, Shulman GI, Zawalich W, DeFronzo RA. Effect of chronic hyperglycemia on in vivo insulin secretion in partially pancreatectomized rats. J Clin Invest 1987;80:1037-1044.

42. McGarry JD, Dobbins RL. Fatty acids, lipotoxicity and insulin secretion. Diabetologia 1999;42:128-138.

43. Prentki M, Joly E, El-Assaad W, Roduit R. Malonyl-CoA signaling, lipid partitioning, and glucolipotoxicity: role in beta-cell adaptation and failure in the etiology of diabetes. Diabetes 2002;51 (Suppl 3):S405-S413.

44. Poitout V, Robertson RP. Minireview: Secondary beta-cell failure in type 2 diabetes-a convergence of glucotoxicity and lipotoxicity. Endocrinology 2002;143:339-342.

45. Martin BC, Warram JH, Krolewski AS, Bergman RN, Soeldner JS, Kahn CR. Role of glucose and insulin resistance in development of type 2 diabetes mellitus: results of a 25-year follow-up study. Lancet 1992;340:925-929.

46. Brunzell JD, Robertson RP, Lerner RL, et al. Relationships between fasting plasma glucose levels and insulin secretion during intravenous glucose tolerance tests. J Clin Endocrinol Metab 1976;42:222-229.

47. Gerich JE. The genetic basis of type 2 diabetes mellitus: Impaired insulin secretion versus impaired insulin sensitivity. Endo Revs 1998;19:491-503.

48. Perley MJ, Kipnis DM. Plasma insulin responses to oral and intravenous glucose: studies in normal and diabetic subjects. J Clin Invest 1967;46:1954-1962

49. Lillioja S, Mott DM, Howard BV, 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.

50. Lillioja S, Mott DM, Spraul M, et al. Insulin resistance and insulin secretory dysfunction as precursors of non-insulin-dependent diabetes mellitus. Prospective studies of Pima Indians. N Engl J Med 1993;329:1988-1992.

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. Bergman RN, Phillips LS, Cobelli C. Physiologic evaluation of factors controlling glucose tolerance in man: measurement of insulin sensitivity and beta-cell glucose sensitivity from the response to intravenous glucose. J Clin Invest 1981;68:1456-1467.

53. Kahn SE, Prigeon RL, McCulloch DK, et al. Quantification of the relationship between insulin sensitivity and beta-cell function in human subjects. Evidence for a hyperbolic function. Diabetes 1993;42:1663-1672.

54. Cavaghan MK, Ehrmann DA, Polonsky KS. Interactions between insulin resistance and insulin secretion in the development of glucose intolerance. J Clin Invest 2000;106:329-333.

55. Kahn SE. The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of Type 2 diabetes. Diabetologia 2003;46:3-19.

56. 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;104:787-794.

57. Gastaldelli A, Ferrannini E, Miyazaki Y, Matsuda M, DeFronzo RA; San Antonio metabolism study. Beta-cell dysfunction and glucose intolerance: results from the San Antonio metabolism (SAM) study. Diabetologia 2004;47:31-39.

58. 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

59. Fukushima M, Usami M, Ikeda M, et al. Insulin secretion and insulin sensitivity at different stages of glucose tolerance: a cross-sectional study of Japanese type 2 diabetes. Metabolism 2004;53:831-835.

60. Osei K, Rhinesmith S, Gaillard T, Schuster D. Impaired insulin sensitivity, insulin secretion, and glucose effectiveness, predict future development of impaired glucose tolerance and type 2 diabetes in pre-diabetic African Americans: implications for primary diabetes prevention. Diabetes Care 2004;27:1439-1446.

61. Piche ME, Arcand-Bosse JF, Despres JP, Perusse L, Lemieux S, Weisnagel SJ. What is a normal glucose value? Differences in indexes of plasma glucose homeostasis in subjects with normal fasting glucose. Diabetes Care 2004;27:2470-2477.

62. Tirosh A, Shai I, Tekes-Manova D, et al. Normal fasting plasma glucose levels and type 2 diabetes in young men. N Engl J Med. 2005;353:1454-1462.

63. Weir GC. Non-insulin-dependent diabetes mellitus: interplay between B-cell inadequacy and insulin resistance. Am J Med 1982;73:461-464.

64. 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;51:2796-2803.

65. Xiang AH, Peters RK, Kjos SL, et al. Effect of pioglitazone on pancreatic beta-cell function and diabetes risk in Hispanic women with prior gestational diabetes. Diabetes. 2006;55:517-522.

66. Leahy JL. ß-cell dysfunction in type 2 diabetes mellitus. In: Kahn CR, editor. Joslin's Diabetes Mellitus, 14th edition. Lippincott Williams & Wilkins; 2005:449-461.

67. Porksen N. The in vivo regulation of pulsatile insulin secretion. Diabetologia 2002;45:3-20.

68. Meier JJ, Kjems LL, Veldhuis JD, Lefebvre P, Butler PC. Postprandial suppression of glucagon secretion depends on intact pulsatile insulin secretion: further evidence for the intraislet insulin hypothesis. Diabetes. 2006;55:1051-1056.

69. Polonsky KS, Sturis J, Van Cauter. Temporal profiles and clinical significance of pulsatile insulin secretion. Horm Res 1998;49: 178-184.

70. O'Rahilly S, Turner RC, Matthews DR. Impaired pulsatile secretion of insulin in relatives of patients with non-insulin-dependent diabetes. N Engl J Med 1988;318:1225-1230.

71. Schmitz O, Porksen N, Nyholm B, et al. Disorderly and nonstationary insulin secretion in relatives of patients with NIDDM. Am J Physiol 1997;272:E218-E226.

72. Calles-Escandon J, Robbins DC. Loss of early phase of insulin release in humans impairs glucose tolerance and blunts thermic effect of glucose. Diabetes 1987;36:1167-1172.

73. Luzi L, DeFronzo RA. 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.

74. Bruce DG, Chisholm DJ, Storlien LH, Kraegen EW. Physiological importance of deficiency in early prandial insulin secretion in non-insulin-dependent diabetes. Diabetes 1988;37:736-744.

75. Vague P, Moulin JP. The defective glucose sensitivity of the B cell in non insulin dependent diabetes. Improvement after twenty hours of normoglycaemia. Metabolism 1982;31:139-142.

76. 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;281:2005-2012.

77. 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.

78. Yoon KH, Ko SH, Cho JH, et al. Selective beta-cell loss and alpha-cell expansion in patients with type 2 diabetes mellitus in Korea. J Clin Endocrinol Metab 2003;88:2300-2308.

79. Leahy JL, Bonner-Weir S, Weir GC. Minimal chronic hyperglycemia is a critical determinant of impaired insulin secretion after an incomplete pancreatectomy. J Clin Invest 1988;81:1407-1414.

80. Opie EL. The relation of diabetes mellitus to lesions of the pancreas: hyaline degeneration of the islands of Langerhans. J Exp Med 1900-1901;5:527-540.

81. Westermark P, Wernstedt C, Wilander E, Hayden DW, O'Brien TD, Johnson KH. Amyloid fibrils in human insulinoma and islets of Langerhans of the diabetic cat are derived from a neuropeptide-like protein also present in normal islet cells. Proc Natl Acad Sci 1987;84:3881-3885.

82. 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 1987;84:8628-8632.

83. Janson J, Soeller WC, Roche PC, et al. Spontaneous diabetes mellitus in transgenic mice expressing human islet amyloid polypeptide. Proc Natl Acad Sci 1996;93:7283-7288.

84. Verchere CB, D'Alessio DA, Palmiter RD, et al. Islet amyloid formation associated with hyperglycemia in transgenic mice with pancreatic beta cell expression of human islet amyloid polypeptide. Proc Natl Acad Sci 1996;93:3492-3496.

85. Hoppener JW, Ahren B, Lips CJ. Islet amyloid and type 2 diabetes mellitus. N EnglJ Med 2000;343:411-419.

86. Lorenzo A, Razzaboni B, Weir GC, Yankner BA. Pancreatic islet cell toxicity of amylin associated with type-2 diabetes mellitus. Nature 1994;368:756-760.

87. Janson J, Ashley RH, Harrison D, McIntyre S, Butler PC. The mechanism of islet amyloid polypeptide toxicity is membrane disruption by intermediate-sized toxic amyloid particles. Diabetes 1999;48:491-498.

88. Butler AE, Janson J, Soeller WC, Butler PC. Increased beta-cell apoptosis prevents adaptive increase in beta-cell mass in mouse model of type 2 diabetes: evidence for role of islet amyloid formation rather than direct action of amyloid. Diabetes 2003;52:2304-2314.

89. O'Brien TD, Butler AE, Roche PC, Johnson KH, Butler PC. Islet amyloid polypeptide in human insulinomas. Evidence for intracellular amyloidogenesis. Diabetes 1994;43:329-336.

90. Marchetti P, Del Guerra S, Marselli L, 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.

91. Harding HP, Ron D. Endoplasmic reticulum stress and the development of diabetes: a review. Diabetes 2002;51 Suppl 3:S455-S461.

92. Donath MY, Storling J, Maedler K, Mandrup-Poulsen T. Inflammatory mediators and islet beta-cell failure: a link between type 1 and type 2 diabetes. J Mol Med 2003;81:455-470.

93. Donath MY, Halban PA. Decreased beta-cell mass in diabetes: significance, mechanisms and therapeutic implications. Diabetologia 2004;47:581-589.

94. 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.

95. Schrauwen P, Hesselink MK. Oxidative capacity, lipotoxicity, and mitochondrial damage in type 2 diabetes. Diabetes 2004;53: 1412-1417.

96. Deng S, Vatamaniuk M, Huang X, et al. Structural and functional abnormalities in the islets isolated from type 2 diabetic subjects. Diabetes 2004;53:624-632.

97. Del Guerra S, Lupi R, Marselli L, et al. Functional and molecular defects of pancreatic islets in human type 2 diabetes. Diabetes 2005;54:727-735.

98. Anello M, Lupi R, Spampinato D, et al. Functional and morphological alterations of mitochondria in pancreatic beta cells from type 2 diabetic patients. Diabetologia 2005;48:282-289.

99. Ostenson CG, Gaisano H, Sheu L, Tibell A, Bartfai T. Impaired gene and protein expression of exocytotic soluble N-ethylmaleimide attachment protein receptor complex proteins in pancreatic islets of type 2 diabetic patients. Diabetes 2006;55:435-440.

100. Leahy JL. Detrimental effects of chronic hyperglycemia on the pancreatic ß-cell. In: LeRoith D, Olefsky JM, Taylor S, editors. Diabetes Mellitus: A Fundamental and Clinical Text. Philadelphia, PA, USA: Lippincott;2004: 115-127.

101. Jonas JC, Sharma A, Hasenkamp W, et al. Chronic hyperglycemia triggers loss of pancreatic beta cell differentiation in an animal model of diabetes. J Biol Chem 1999;274:14112-14121.

102. Laybutt DR, Sharma A, Sgroi DC, Gaudet J, Bonner-Weir S, Weir GC. Genetic regulation of metabolic pathways in beta-cells disrupted by hyperglycemia. J Biol Chem 2002;277:10912-10921.

103. Leahy JL. ß-cell dysfunction with chronic hyperglycemia: the "overworked ß-cell" hypothesis. Diabetes Revs 1996;4:298-319.

104. Greenwood RH, Mahler RF, Hales CN. Improvement in insulin secretion in diabetes after diazoxide. Lancet 1976;1:444-447.

105. Laedtke T, Kjems L, Porksen N, Schmitz O, Veldhuis J, Kao PC, Butler PC. Overnight inhibition of insulin secretion restores pulsatility and proinsulin/insulin ratio in type 2 diabetes. Am J Physiol Endocrinol Metab 2000;279:E520-E528.

106. Song SH, Rhodes CJ, Veldhuis JD, Butler PC. Diazoxide attenuates glucose-induced defects in first-phase insulin release and pulsatile insulin secretion in human islets. Endocrinology 2003;144:3399-3405.

107. Olson LK, Qian J, Poitout V. Glucose rapidly and reversibly decreases INS-1 cell insulin gene transcription via decrements in STF-1 and C1 activator transcription factor activity. Mol Endocrinol 1998;12:207-219.

108. 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;280:32,413-32,418.

109. Unger RH. Lipotoxicity in the pathogenesis of obesity-dependent NIDDM. Genetic and clinical implications. Diabetes 1995;44: 863-870.

110. Liu YQ, Tornheim K, Leahy JL. Glucose-fatty acid cycle to inhibit glucose utilization and oxidation is not operative in fatty acid-cultured islets. Diabetes 1999;48:1747-1753.

111. MacDonald MJ, Fahien LA, Brown LJ, Hasan NM, Buss JD, Kendrick MA. Perspective: emerging evidence for signaling roles of mitochondrial anaplerotic products in insulin secretion. Am J Physiol Endocrinol Metab 2005;288:E1-E15.

112. Liu YQ, Jetton TL, Leahy JL Beta-cell adaptation to insulin resistance. Increased pyruvate carboxylase and malate-pyruvate shuttle activity in islets of nondiabetic Zucker fatty rats. J Biol Chem 2002;277:39,163-39,168.

113. Nolan CJ, Leahy JL, Delghingaro-Augusto V, et al. Beta cell compensation for insulin resistance in Zucker fatty rats: increased lipolysis and fatty acid signalling. Diabetologia 2006;49:2120-2130

114. Nauck MA, Meier JJ. Glucagon-like peptide 1 and its derivatives in the treatment of diabetes. Regul Pept 2005;128:135-148.

115. Hansotia T, Drucker DJ. GIP and GLP-1 as incretin hormones: lessons from single and double incretin receptor knockout mice. Regul Pept 2005;128:125-134.

116. Holst JJ. Glucagon-like peptide-1: from extract to agent. The Claude Bernard Lecture, 2005. Diabetologia 2006;49:253-260.

117. Nauck MA, Heimesaat MM, Orskov C, et al. Preserved incretin activity of glucagon-like peptide 1 [7-36 amine] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus. J Clin Invest 1993;91:301-307.

118. Meier JJ, Hücking 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.

119. Meier JJ, Gallwitz B, Askenas M, et al. Secretion of incretin hormones and the insulinotropic effect of gastric inhibitory polypeptide in women with a history of gestational diabetes. Diabetologia 2005;48:1872-1881.

120. Holst JJ, Gromada J, Nauck MA. The pathogenesis of NIDDM involves a defective expression of the GIP receptor. Diabetologia 1997;40:984-986.

121. Vilsboll T, Krarup T, Deacon CF, Madsbad S, Holst JJ. Reduced postprandial concentrations of intact biologically active glucagons-like peptide 1 in type 2 diabetic patients. Diabetes 2001;50:609-613.

122. DeFronzo RA. Pathogenesis of type 2 diabetes mellitus. Med Clin N Am 2004;88:787-835.

123. Petersen KF, Shulman GI. Etiology of insulin resistance. Am J Med 2006;119(Suppl 1):S10-S16.

124. Pratipanawatr W, Pratipanawatr T, Cusi K, et al. Skeletal muscle insulin resistance in normoglycemic subjects with a strong family history of type 2 diabetes is associated with decreased insulin-stimulated insulin receptor substrate-1 tyrosine phosphorylation. Diabetes 2001;50:2572-2578.

125. Qiao LY, Goldberg JL, Russell JC, Sun XJ. Identification of enhanced serine kinase activity in insulin resistance. J Biol Chem 1999;274:10,625-10,632.

126. Aguirre V, Werner ED, Giraud J, Lee YH, Shoelson SE, White MF. Phosphorylation of Ser307 in insulin receptor substrate-1 blocks interactions with the insulin receptor and inhibits insulin action. J Biol Chem 2002;277:1531-1537.

127. Gual P, Le Marchand-Brustel Y, Tanti JF. Positive and negative regulation of insulin signaling through IRS-1 phosphorylation. Biochimie 2005;87:99-109.

128. Tzatsos A, Kandror KV. Nutrients suppress phosphatidylinositol 3-kinase/Akt signaling via raptor-dependent mTOR-mediated insulin receptor substrate 1 phosphorylation. Mol Cell Biol 2006;26:63-76.

129. Zhande R, Mitchell JJ, Wu J, Sun XJ. Molecular mechanism of insulin-induced degradation of insulin receptor substrate 1. Mol Cell Biol 2002;22:1016-1026.

130. Marshall S, Bacote V, Traxinger RR. Discovery of a metabolic pathway mediating glucose-induced desensitization of the glucose transport system. Role of hexosamine biosynthesis in the induction of insulin resistance. J Biol Chem 1991;266:4706-4712.

131. Veerababu G, Tang J, Hoffman RT, et al. Overexpression of glutamine: fructose-6-phosphate amidotransferase in the liver of transgenic mice results in enhanced glycogen storage, hyperlipidemia, obesity, and impaired glucose tolerance. Diabetes 2000;49:2070-2078.

132. Spampinato D, Giaccari A, Trischitta V, et al. Rats that are made insulin resistant by glucosamine treatment have impaired skeletal muscle insulin receptor phosphorylation. Metabolism. 2003;52:1092-1095.

133. Wells L, Vosseller K, Hart GW. A role for N-acetylglucosamine as a nutrient sensor and mediator of insulin resistance. Cell Mol Life Sci 2003;60:222-228.

134. Buse MG. Hexosamines, insulin resistance, and the complications of diabetes: current status. Am J Physiol Endocrinol Metab 2006;290:E1-E8.

135. Petersen KF, Dufour S, Befroy D, Garcia R, Shulman GI. Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes. N Engl J Med 2004;350:664-671.

136. Goodpaster BH, Kelley DE Skeletal muscle triglyceride: marker or mediator of obesity-induced insulin resistance in type 2 diabetes mellitus? CurrDiab Rep 2002;2:216-222.

137. Yki-Jarvinen H. Fat in the liver and insulin resistance. Ann Med 2005;37:347-356.

138. Nyholm B, Qu Z, Kaal A, et al. Evidence of an increased number of type 11b muscle fibers in insulin-resistant first-degree relatives of patients with NIDDM. Diabetes 1997;46:1822-1828.

139. Kelley DE, He J, Menshikova EV, Ritov VB. Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes. Diabetes 2002;51:2944-2950.

140. Menshikova EV, Ritov VB, Toledo FG, Ferrell RE, Goodpaster BH, Kelley DE. Effects of weight loss and physical activity on skeletal muscle mitochondrial function in obesity. Am J Physiol Endocrinol Metab 2005;288:E818-E825.

141. Sparks LM, Xie H, Koza RA, Mynatt R, Hulver MW, Bray GA, Smith SR. A high-fat diet coordinately downregulates genes required for mitochondrial oxidative phosphorylation in skeletal muscle. Diabetes 2005;54:1926-1933.

142. Boden G, Chen X, Rosner J, Barton M. Effects of a 48-h fat infusion on insulin secretion and glucose utilization. Diabetes 1995;44:1239-1242.

143. Boden G, Cheung P, Stein TP, Kresge K, Mozzoli M. FFA cause hepatic insulin resistance by inhibiting insulin suppression of glycogenolysis. Am J Physiol Endocrinol Metab 2002;283:E12-E19.

144. Boden G, Carnell LH. Nutritional effects of fat on carbohydrate metabolism. Best Pract Res Clin Endocrinol Metab 2003;17:399-410.

145. Kim JK, Fillmore JJ, Sunshine MJ, et al. PKC-theta knockout mice are protected from fat-induced insulin resistance. J Clin Invest 2004;114:823-827.

146. Perseghin G, Petersen K, Shulman GI. Cellular mechanism of insulin resistance: potential links with inflammation. Int J Obes Relat Metab Disord 2003;27 Suppl 3:S6-S11.

147. Ueki K, Kondo T, Kahn CR. Suppressor of cytokine signaling 1 (SOCS-1) and SOCS-3 cause insulin resistance through inhibition of tyrosine phosphorylation of insulin receptor substrate proteins by discrete mechanisms. Mol Cell Biol 2004;24:5434-5446.

148. Yuan M, Konstantopoulos N, Lee J, Hansen L, Li ZW, Karin M, Shoelson SE. Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta. Science 2001;293:1673-1677.

149. Saha AK, Ruderman NB. Malonyl-CoA and AMP-activated protein kinase: an expanding partnership. Mol Cell Biochem 2003;253: 65-70.

150. Zou MH, Kirkpatrick SS, Davis BJ, et al. Activation of the AMP-activated protein kinase by the anti-diabetic drug metformin in vivo. Role of mitochondrial reactive nitrogen species. J Biol Chem 2004;279:43,940-43,951.

151. Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 2004;89:2548-2556.

152. Borst SE. The role of TNF-alpha in insulin resistance. Endocrine 2004;23:177-182.

153. Haluzik M, Parizkova J, Haluzik MM. Adiponectin and its role in the obesity-induced insulin resistance and related complications. Physiol Res 2004;53:123-129.

154. Gil-Campos M, Canete RR, Gil A. Adiponectin, the missing link in insulin resistance and obesity. Clin Nutr 2004;23:963-974.

155. Kadowaki T, Yamauchi T. Adiponectin and adiponectin receptors. Endocr Rev 2005;26:439-451.

156. Yang Q, Graham TE, Mody N, et al. Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature 2005;436:356-362.

157. Steppan CM, Bailey ST, Bhat S, et al. The hormone resistin links obesity to diabetes. Nature 2001;409:307-312.

158. Hotamisligil, GS. The irresistible biology of resistin. J Clin Invest 2003;111:173-174.

159. Banerjee RR, Rangwala SM, Shapiro JS, et al. Regulation of fasted blood glucose by resistin. Science 2004;303:1195-1198.

160. Satoh H, Nguyen MT, Miles PDG, Imamura T, Usui I, Olefsky JM. Adenovirus-mediated chronic "hyper-resistinemia" leads to in vivo insulin resistance in normal rats. J Clin Invest 2004;114:224-231.

161. Muse ED, Obici S, Bhanot S, et al. Role of resistin in diet-induced hepatic insulin resistance. J Clin Invest 2004; 114:232-239.

162. Rangwala SM, Rich AS, Rhoades B, Shapiro JS, Obici S, Rossetti L, Lazar MA. Abnormal glucose homeostasis due to chronic hyperresistinemia. Diabetes 2004;53:1937-1941.

163. McCarthy MI, Zeggini E. Genome-wide association scans for Type 2 diabetes: new insights into biology and therapy. Trends Pharmacol Sci 2007;28:598-601.

Lose 10 Pounds Naturally

Lose 10 Pounds Naturally

Studies show obesity may soon overtake tobacco as the leading cause of death in America. Are you ready to drop those extra pounds you've been carrying around? Awesome. Let's start off with a couple positive don't. You don't need to jump on a diet craze and you don't need to start exercising for hours each day.

Get My Free Ebook


Post a comment