1. Stumvoll M, Goldstein BJ, Van Haeften TW. Type 2 diabetes: principles of pathogenesis and therapy. Lancet 2005; 365:1333-46.

2. Bergman RN. Lilly lecture 1989. Toward physiological understanding of glucose tolerance. Minimalmodel approach. Diabetes 1989; 38:1512-27.

3. 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; 104:787-94.

4. Stumvoll M, Tataranni PA, Stefan N, Vozarova B, Bogardus C. Glucose allostasis. Diabetes 2003; 52: 903-9.

5. Dinneen S, Gerich J, Rizza R. Carbohydrate metabolism in non-insulin-dependent diabetes mellitus. N Engl J Med 1992; 327:707-13.

6. Weyer C, Bogardus C, Pratley RE. Metabolic characteristics of individuals with impaired fasting glucose and/or impaired glucose tolerance. Diabetes 1999; 48:2197-203.

7. Meyer C, Stumvoll M, Nadkarni V, Dostou J, Mitrakou A, Gerich J. Abnormal renal and hepatic glucose metabolism in type 2 diabetes mellitus. J Clin Invest 1998; 102:619-24.

8. Boden G. Role of fatty acids in the pathogenesis of insulin resistance and NIDDM. Diabetes 1997; 46: 3-10.

9. Bruning JC, Michael MD, Winnay JN, et al. A muscle-specific insulin receptor knockout exhibits features of the metabolic syndrome of NIDDM without altering glucose tolerance. Mol Cell 1998; 2: 559-69.

10. Bluher M, Kahn BB, Kahn CR. Extended longevity in mice lacking the insulin receptor in adipose tissue. Science 2003; 299:572-4.

11. Michael MD, Kulkarni RN, Postic C, et al. Loss of insulin signaling in hepatocytes leads to severe insulin resistance and progressive hepatic dysfunction. Mol Cell 2000; 6:87-97.

12. Kulkarni RN, Bruning JC, Winnay JN, Postic C, Magnuson MA, Kahn CR. Tissue-specific knockout of the insulin receptor in pancreatic beta cells creates an insulin secretory defect similar to that in type 2 diabetes. Cell 1999; 96:329-39.

13. Kido Y, Nakae J, Accili D. Clinical review 125: the insulin receptor and its cellular targets. J Clin Endocrinol Metab 2001; 86:972-9.

14. White MF. IRS proteins and the common path to diabetes. Am J Physiol Endocrinol Metab 2002; 283: E413-22.

15. Zick Y. Insulin resistance: a phosphorylation-based uncoupling of insulin signaling. Trends Cell Biol 2001; 11:437-41.

16. Goldstein BJ. Protein-tyrosine phosphatases and the regulation of insulin action. In: LeRoith D, Taylor SI, Olefsky JM, eds. Diabetes mellitus: A Fundamental and Clinical Text. Philadelphia: Lippincott, 2003:255-68.

17. Zhande R, Mitchell JJ, Wu J, Sun XJ. Molecular mechanism of insulin-induced degradation of insulin receptor substrate 1. Mol Cell Biol 2002; 22:1016-26.

18. Rui L, Yuan M, Frantz D, Shoelson S, White MF. SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2. J Biol Chem 2002; 277:42394-8.

19. Rajala MW, Scherer PE. Mini review: the adipocyte—at the crossroads of energy homeostasis, inflammation, and atherosclerosis. Endocrinology 2003; 144:3765-73.

20. Ravussin E, Smith SR. Increased fat intake, impaired fat oxidation, and failure of fat cell proliferation result in ectopic fat storage, insulin resistance, and type 2 diabetes mellitus. Ann NY Acad Sci 2002; 967:363-78.

21. Boden G, Shulman GI. Free fatty acids in obesity and type 2 diabetes: defining their role in the development of insulin resistance and b-cell dysfunction. Eur J Clin Invest 2002; 32(Suppl. 3):14-23.

22. Shulman GI. Cellular mechanisms of insulin resistance. J Clin Invest 2002; 106:171-6.

23. Griffin ME, Marcucci MJ, Cline GW, et al. Free fatty acid-induced insulin resistance is associated with activation of protein kinase C theta and alterations in the insulin signaling cascade. Diabetes 1999; 48:1270-4.

24. Itani SI, Ruderman NB, Schmieder F, Boden G. Lipid-induced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C, and I kappa B-alpha. Diabetes 2002; 51:2005-11.

25. Gao Z, Zhang X, Zuberi A, et al. Inhibition of insulin sensitivity by free fatty acids requires activation of multiple serine kinases in 3T3-L1 adipocytes. Mol Endocrinol 2004; 18:2024-34.

26. Hotamisligil GS. Molecular mechanisms of insulin resistance and the role of the adipocyte. Int J Obes Relat Metab Disord 2000; 24(Suppl. 4):S23-7.

27. Moller DE. Potential role of TNF-alpha in the pathogenesis of insulin resistance and type 2 diabetes. Trends Endocrinol Metab 2000; 11:212-7.

28. Senn JJ, Klover PJ, Nowak IA, et al. Suppressor of cytokine signaling-3 (SOCS-3), a potential mediator of interleukin-6-dependent insulin resistance in hepatocytes. J Biol Chem 2003; 278: 13740-6.

29. Krebs DL, Hilton DJ. A new role for SOCS in insulin action. Suppressor of cytokine signaling. Sci STKE 2003:E6.

30. Goldstein BJ, Scalia R. Adiponectin: a novel adipokine linking adipocytes and vascular function. J Clin Endocrinol Metab 2004; 89:2563-8.

31. Yamauchi T, Kamon J, Minokoshi Y, et al. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 2002; 8:1288-95.

32. Tomas E, Tsao TS, Saha AK, et al. Enhanced muscle fat oxidation and glucose transport by ACRP30 globular domain: acetyl-CoA carboxylase inhibition and AMP-activated protein kinase activation. Proc Natl Acad Sci USA 2002; 99:16309-13.

33. Wu X, Motoshima H, Mahadev K, Stalker TJ, Scalia R, Goldstein BJ. Involvement of AMP-activated protein kinase in glucose uptake stimulated by the globular domain of adiponectin in primary rat adipocytes. Diabetes 2003; 52:1355-63.

34. Ruderman NB, Cacicedo JM, Itani S, et al. Malonyl-CoA and AMP-activated protein kinase (AMPK): possible links between insulin resistance in muscle and early endothelial cell damage in diabetes. Biochem Soc Trans 2003; 31:202-6.

35. Karin M, Delhase M. The I kappa B kinase (IKK) and NF-kappa B: Key elements of proinflammatory signalling. Semin Immunol 2000; 12:85-98.

36. Yin MJ, Yamamoto Y, Gaynor RB. The anti-inflammatory agents aspirin and salicylate inhibit the activity of I (kappa) B kinase-beta. Nature 1998; 396:77-80.

37. Kim JK, Kim YJ, Fillmore JJ, et al. Prevention of fat-induced insulin resistance by salicylate. J Clin Invest 2001; 108:437-46.

38. Yuan M, Konstantopoulos N, Lee J, et al. Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta. Science 2001; 293:1673-7.

39. Shoelson SE, Lee J, Yuan M. Inflammation and the IKK beta/I kappa B/NF-kappa B axis in obesity-and diet-induced insulin resistance. Int J Obes Relat Metab Disord 2003; 27(Suppl. 3):S49-52.

40. Havel PJ. Control of energy homeostasis and insulin action by adipocyte hormones: leptin, acylation stimulating protein, and adiponectin. Curr Opin Lipidol 2002; 13:51-9.

41. Wellen KE, Hotamisligil GS. Obesity-induced inflammatory changes in adipose tissue. J Clin Invest 2003; 112:1785-8.

42. Kelley DE, He J, Menshikova EV, Ritov VB. Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes. Diabetes 2002; 51:2944-50.

43. 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; 350:664-71.

44. Patti ME, Butte AJ, Crunkhorn S, et al. Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: potential role of PGC1 and NRF1. Proc Natl Acad Sci USA 2003; 100:8466-71.

45. Mootha VK, Lindgren CM, Eriksson KF, et al. PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately down regulated in human diabetes. Nat Genet 2003; 34:267-73.

46. Hopkins DF, Williams G. Insulin receptors are widely distributed in human brain and bind human and porcine insulin with equal affinity. Diab Med 1997; 14:1044-50.

47. Boyd FT, Clarke DW, Muther TF, Raizada MK. Insulin receptors and insulin modulation of norepinephrine uptake in neuronal cultures from rat brain. J Biol Chem 1985; 15:15880-4.

48. Woods S, Lotter E, McKay L, Porte DJ. Chronic intracerebroventricular infusion of insulin reduces food intake and body weight of baboons. Nature 1979; 282:503-5.

49. Porte D Jr, Seeley RJ, Woods SC, Baskin DG, Figlewicz DP, Schwartz MW. Obesity, diabetes and the central nervous system. Diabetologia 1998; 41:863-81.

50. Bruning JC, Gautam D, Burks DJ, et al. Role of brain insulin receptor in control of body weight and reproduction. Science 2000; 289:2122-5.

51. Hallschmid M, Benedict C, Schultes B, Fehm HL, Born J, Kern W. Intranasal insulin reduces body fat in men but not in women. Diabetes 2004; 53:3024-9.

52. Tschritter O, Preissl H, Hennige AM, et al. The cerebrocortical response to hyperinsulinemia is reduced in overweight humans: a magneto encephalographic study. Proc Natl Acad Sci USA 2006.

53. Gerich JE. The genetic basis of type 2 diabetes mellitus: impaired insulin secretion versus impaired insulin sensitivity. Endocr Rev 1998; 19:491-503.

54. Pimenta W, Korytkowski M, Mitrakou A, et al. Pancreatic beta-cell dysfunction as the primary genetic lesion in NIDDM. JAMA 1995; 273:1855-61.

55. Yki-Jarvinen H. Glucose toxicity. Endocr Rev 1992; 13:415-31.

56. Robertson RP, Harmon J, Tran PO, Tanaka Y, Takahashi H. Glucose toxicity in beta-cells: type 2 diabetes, good radicals gone bad, and the glutathione connection. Diabetes 2003; 52:581-7.

57. Patane G, Anello M, Piro S, Vigneri R, Purrello F, Rabuazzo AM. Role of ATP production and uncoupling protein-2 in the insulin secretory defect induced by chronic exposure to high glucose or free fatty acids and effects of peroxisome proliferator-activated receptor-gamma inhibition. Diabetes 2002; 51:2749-56.

58. 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):S119-24.

59. Shimabukuro M, Zhou YT, Lee Y, Unger RH. Troglitazone lowers islet fat and restores beta cell function of diabetic fatty rats. J Biol Chem 1998; 273:3547-50.

60. Chavez JA, Holland WL, Bar J, Sandhoff K, Summers SA. Acid ceramidase over expression prevents the inhibitory effects of saturated fatty acids on insulin signaling. J Biol Chem 2005; 280:20148-53.

61. Kelpe CL, Moore PC, Parazzoli SD, Wicksteed B, Rhodes CJ, Poitout V. Palmitate inhibition of insulin gene expression is mediated at the transcriptional level via ceramide synthesis. J Biol Chem 2003; 278:30015-21.

62. Haber EP, Ximenes HM, Procopio J, Carvalho CR, Curi R, Carpinelli AR. Pleiotropic effects of fatty acids on pancreatic beta-cells. J Cell Physiol 2003; 194:1-12.

63. Hoppener JW, Ahren B, Lips CJ. Islet amyloid and type 2 diabetes mellitus. N Engl J Med 2000; 343: 411-9.

64. 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; 89:3629-43.

65. Knowles NG, Landchild MA, Fujimoto WY, Kahn SE. Insulin and amylin release are both diminished in first-degree relatives of subjects with type 2 diabetes. Diabetes Care 2002; 25:292-7.

66. Pierce M, Keen H, Bradley C. Risk of diabetes in offspring of parents with non-insulin-dependent diabetes. Diabet Med 1995; 12:6-13.

67. Tattersal RB, Fajans SS. Prevalence of diabetes and glucose intolerance in 199 offspring of thirty-seven conjugal diabetic parents. Diabetes 1975; 24:452-62.

68. Kaprio J, Tuomilehto J, Koskenvuo M, et al. Concordance for type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus in a population-based cohort of twins in Finland. Diabetologia 1992; 35:1060-7.

69. Newman B, Selby JV, King MC, Slemenda C, Fabsitz R, Friedman GD. Concordance for type 2 (non-insulin-dependent) diabetes mellitus in male twins. Diabetologia 1987; 30:763-8.

70. Hales CN, Barker DJ. Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Diabetologia 1992; 35:595-601.

71. Hattersley AT, Tooke JE. The fetal insulin hypothesis: an alternative explanation of the association of low birth weight with diabetes and vascular disease. Lancet 1999; 353:1789-92.

72. Parikh H, Groop L. Candidate genes for type 2 diabetes. Rev Endocrinol Metab Disord 2004; 5: 151-76.

73. Lohmueller KE, Pearce CL, Pike M, Lander ES, Hirschhorn JN. Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease. Nat Genet 2003; 33:177-82.

74. Olefsky JM. Treatment of insulin resistance with peroxisome proliferator-activated receptor gamma agonists. J Clin Invest 2000; 106:467-72.

75. Schoonjans K, Auwerx J. Thiazolidinediones: an update. Lancet 2000; 355:1008-10.

76. Auwerx J. PPARgamma, the ultimate thrifty gene. Diabetologia 1999; 42:1033-49.

77. Memisoglu A, Hu FB, Hankinson SE, et al. Prospective study of the association between the proline to alanine codon 12 polymorphism in the PPARgamma gene and type 2 diabetes. Diabetes Care 2003; 26:2915-7.

78. Silander K, Mohlke KL, Scott LJ, et al. Genetic variation near the hepatocyte nuclear factor-4 alpha gene predicts susceptibility to type 2 diabetes. Diabetes 2004; 53:1141-9.

79. 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; 52:568-72.

80. Cox NJ. Challenges in identifying genetic variation affecting susceptibility to type 2 diabetes: examples from studies of the calpain-10 gene. Hum Mol Genet 2001; 10:2301-5.

81. 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; 26:163-75.

82. Tsuchiya T, Schwarz PE, Bosque-Plata LD, et al. Association of the calpain-10 gene with type 2 diabetes in Europeans: results of pooled and meta-analyses. Mol Genet Metab 2006.

83. Baier LJ, Permana PA, Yang X, et al. A calpain-10 gene polymorphism is associated with reduced muscle mRNA levels and insulin resistance. J Clin Invest 2000; 106:R69-73.

84. Sreenan SK, Zhou YP, Otani K, et al. Calpains play a role in insulin secretion and action. Diabetes 2001; 50:2013-20.

85. Arrington D, Van Vleet T, Schnellmann R. Calpain 10: a mitochondrial calpain and its role in calcium-induced mitochondrial dysfunction. Am J Physiol Cell Physiol 2006.

86. Meyre D, Bouatia-Naji N, Tounian A, et al. Variants of ENPP1 are associated with childhood and adult obesity and increase the risk of glucose intolerance and type 2 diabetes. Nat Genet 2005; 37: 863-7.

87. Abate N, Chandalia M, Satija P, et al. ENPP1/PC-1 K121Q polymorphism and genetic susceptibility to type 2 diabetes. Diabetes 2005; 54:1207-13.

88. Matsuoka N, Patki A, Tiwari HK, et al. Association of K121Q polymorphism in ENPP1 (PC-1) with BMI in Caucasian and African-American adults. Int J Obes (Lond) 2006; 30:233-7.

89. 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; 38:320-3.

90. Florez JC, Jablonski KA, Bayley N, et al. TCF7L2 polymorphisms and progression to diabetes in the Diabetes Prevention Program. N Engl J Med 2006; 355:241-50.

91. Vaxillaire M, Dechaume A, Vasseur-Delannoy V, et al. Genetic analysis of ADIPOR1 and ADIPOR2 candidate polymorphisms for type 2 diabetes in the Caucasian population. Diabetes 2006; 55:856-61.

The Mediterranean Diet Meltdown

The Mediterranean Diet Meltdown

Looking To Lose Weight But Not Starve Yourself? Revealed! The Secret To Long Life And Good Health Is In The Foods We Eat. Download today To Discover The Reason Why The Mediterranean Diet Will Help You Have Great Health, Enjoy Life And Live Longer.

Get My Free Ebook

Post a comment