Glucose toxicity: The leading actor in the pathogenesis and clinical history of type 2 diabetes - mechanisms and potentials for treatment

Nutrition, Metabolism and Cardiovascular Diseases

Volumn 19, Issue 5, 2009, Pages 365-377

  Giaccari, A ^a   Sorice, G ^a   Muscogiuri, G ^a  

^a CATHOLIC UNIVERSITY   (Italy)

Author keywords

Beta cell; Diabetes pathogenesis; Diabetes treatment; Glucose toxicity; Glucotoxicity; Hexosamine; Insulin resistance; Lipotoxicity; Oxidative stress

Indexed keywords

ANTIDIABETIC AGENT; HEXOSAMINE; INSULIN; PROTEIN KINASE C;

CARDIOVASCULAR DISEASE; DIABETES MELLITUS; GLUCOSE BLOOD LEVEL; HUMAN; HYPERGLYCEMIA; METABOLISM; NON INSULIN DEPENDENT DIABETES MELLITUS; OXIDATIVE STRESS; PATHOLOGY; REVIEW; SECONDARY PREVENTION; SECRETION;

BLOOD GLUCOSE; CARDIOVASCULAR DISEASES; DIABETES COMPLICATIONS; DIABETES MELLITUS, TYPE 2; HEXOSAMINES; HUMANS; HYPERGLYCEMIA; HYPOGLYCEMIC AGENTS; INSULIN; OXIDATIVE STRESS; PROTEIN KINASE C; SECONDARY PREVENTION;

EID: 65749113590     PISSN: 09394753     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.numecd.2009.03.018     Document Type: Review

References (130)

1. Haist R.E., Campbell J., and Best C.H. The prevention of diabetes. N Engl J Med 223 (1940) 607-615
2. Robertson R.P., and Porte Jr. D. The glucose receptor. A defective mechanism in diabetes mellitus distinct from the beta adrenergic receptor. J Clin Invest 52 (1973) 870-876
3. Cerasi E., Luft R., and Efendic S. Decreased sensitivity of the pancreatic beta cells to glucose in prediabetic and diabetic subjects. A glucose dose-response study. Diabetes 21 (1972) 224-234
4. Kosaka K., Kuzuya T., Akanuma Y., and Hagura R. Increase in insulin response after treatment of overt maturity-onset diabetes is independent of the mode of treatment. Diabetologia 18 (1980) 23-28
5. Vague P., and Moulin J.P. The defective glucose sensitivity of the B cell in non insulin dependent diabetes. Improvement after twenty hours of normoglycaemia. Metabolism 31 (1982) 139-142
6. Garvey W.T., Olefsky J.M., Griffin J., Hamman R.F., and Kolterman O.G. The effect of insulin treatment on insulin secretion and insulin action in type II diabetes mellitus. Diabetes 34 (1985) 222-234
7. Rossetti L., Shulman G.I., Zawalich W., and DeFronzo R.A. Effect of chronic hyperglycemia on in vivo insulin secretion in partially pancreatectomized rats. J Clin Invest 80 (1987) 1037-1044
8. Rossetti L., Smith D., Shulman G.I., Papachristou D., and DeFronzo R.A. Correction of hyperglycemia with phlorizin normalizes tissue sensitivity to insulin in diabetic rats. J Clin Invest 79 (1987) 1510-1515
9. Kahn B.B., Shulman G.I., DeFronzo R.A., Cushman S.W., and Rossetti L. Normalization of blood glucose in diabetic rats with phlorizin treatment reverses insulin-resistant glucose transport in adipose cells without restoring glucose transporter gene expression. J Clin Invest 87 (1991) 561-570
10. Grill V., Westberg M., and Ostenson C.G. B cell insensitivity in a rat model of non-insulin-dependent diabetes. Evidence for a rapidly reversible effect of previous hyperglycemia. J Clin Invest 80 (1987) 664-669
11. Kim J.K., Zisman A., Fillmore J.J., Peroni O.D., Kotani K., Perret P., et al. Glucose toxicity and the development of diabetes in mice with muscle-specific inactivation of GLUT4. J Clin Invest 108 (2001) 153-160
12. Voyles N.R., Powell A.M., Timmers K.I., Wilkins S.D., Bhathena S.J., Hansen C., et al. Reversible impairment of glucose-induced insulin secretion in SHR/N-cp rats. Genetic model of type II diabetes. Diabetes 37 (1988) 398-404
13. Giroix M.H., Portha B., Kergoat M., Bailbe D., and Picon L. Glucose insensitivity and amino-acid hypersensitivity of insulin release in rats with non-insulin-dependent diabetes. A study with the perfused pancreas. Diabetes 32 (1983) 445-451
14. Davalli A.M., Ricordi C., Socci C., Braghi S., Bertuzzi F., Fattor B., et al. Abnormal sensitivity to glucose of human islets cultured in a high glucose medium: partial reversibility after an additional culture in a normal glucose medium. J Clin Endocrinol Metab 72 (1991) 202-208
15. Bonner-Weir S., Trent D.F., Honey R.N., and Weir G.C. Responses of neonatal rat islets to streptozotocin: limited B-cell regeneration and hyperglycemia. Diabetes 30 (1981) 64-69
16. Bonner-Weir S., Trent D.F., and Weir G.C. Partial pancreatectomy in the rat and subsequent defect in glucose-induced insulin release. J Clin Invest 71 (1983) 1544-1553
17. Leahy J.L., Bonner-Weir S., and Weir G.C. Minimal chronic hyperglycemia is a critical determinant of impaired insulin secretion after an incomplete pancreatectomy. J Clin Invest 81 (1988) 1407-1414
18. Leahy J.L., Cooper H.E., Deal D.A., and Weir G.C. 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 77 (1986) 908-915
19. Nawano M., Oku A., Ueta K., Umebayashi I., Ishirahara T., Arakawa K., et al. Hyperglycemia contributes insulin resistance in hepatic and adipose tissue but not skeletal muscle of ZDF rats. Am J Physiol Endocrinol Metab 278 (2000) E535-E543
20. Portha B., Serradas P., Bailbé D., Suzuki K., Goto Y., and Giroix M.H. Beta-cell insensitivity to glucose in the GK rat, a spontaneous nonobese model for type II diabetes. Diabetes 40 (1991) 486-491
21. Tokuyama Y., Sturis J., DePaoli A.M., Takeda J., Stoffel M., Tang J., et al. Evolution of beta-cell dysfunction in the male Zucker diabetic fatty rat. Diabetes 44 (1995) 1447-1457
22. Donath M.Y., Gross D.J., Cerasi E., and Kaiser N. Hyperglycemia-induced beta-cell apoptosis in pancreatic islets of Psammomys obesus during development of diabetes. Diabetes 48 (1999) 738-744
23. Rossetti L., Giaccari A., and DeFronzo R.A. Glucose toxicity. Diabetes Care 13 (1990) 610-630
24. Leahy J.L., and Weir G.C. Evolution of abnormal insulin secretory responses during 48-h in vivo hyperglycemia. Diabetes 37 (1988) 217-222
25. Marshall S., Bacote V., and Traxinger R.R. 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 266 (1991) 4706-4712
26. Giaccari A., Morviducci L., Zorretta D., Sbraccia P., Leonetti F., Caiola S., et al. In vivo effects of glucosamine on insulin secretion and insulin sensitivity in the rat: possible relevance to the maladaptive responses to chronic hyperglycaemia. Diabetologia 38 (1995) 518-524
27. Robinson K.A., Sens D.A., and Buse M.G. Pre-exposure to glucosamine induces insulin resistance of glucose transport and glycogen synthesis in isolated rat skeletal muscles. Study of mechanisms in muscle and in rat-1 fibroblasts overexpressing the human insulin receptor. Diabetes 42 (1993) 1333-1346
28. Rossetti L., Hawkins M., Chen W., Gindi J., and Barzilai N. In vivo glucosamine infusion induces insulin resistance in normoglycemic but not in hyperglycemic conscious rats. J Clin Invest 96 (1995) 132-140
29. Daniels M.C., Ciaraldi T.P., Nikoulina S., Henry R.R., and McClain D.A. Glutamine:fructose-6-phosphate amidotransferase activity in cultured human skeletal muscle cells: relationship to glucose disposal rate in control and non-insulin-dependent diabetes mellitus subjects and regulation by glucose and insulin. J Clin Invest 97 (1996) 1235-1241
30. Cooksey R.C., and McClain D.A. Transgenic mice overexpressing the rate-limiting enzyme for hexosamine synthesis in skeletal muscle or adipose tissue exhibit total body insulin resistance. Ann N Y Acad Sci 967 (2002 Jun) 102-111
31. Hebert Jr. L.F., Daniels M.C., Zhou J., Crook E.D., Turner R.L., Simmons S.T., et al. Overexpression of glutamine:fructose-6-phosphate amidotransferase in transgenic mice leads to insulin resistance. J Clin Invest 98 (1996) 930-936
32. Veerababu G., Tang J., Hoffman R.T., Daniels M.C., Hebert Jr. L.F., Crook E.D., 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 49 (2000) 2070-2078
33. Tang J., Neidigh J.L., Cooksey R.C., and McClain D.A. Transgenic mice with increased hexosamine flux specifically targeted to beta-cells exhibit hyperinsulinemia and peripheral insulin resistance. Diabetes 49 (2000) 1492-1499
34. Yang X., Ongusaha P.P., Miles P.D., Havstad J.C., Zhang F., So W.V., et al. Phosphoinositide signalling links O-GlcNAc transferase to insulin resistance. Nature 451 (2008) 964-969
35. Vosseller K., Wells L., Lane M.D., and Hart G.W. Elevated nucleocytoplasmic glycosylation by O-GlcNAc results in insulin resistance associated with defects in Akt activation in 3T3-L1 adipocytes. Proc Natl Acad Sci U S A 99 (2002) 5313-5318
36. McClain D.A. Hexosamines as mediators of nutrient sensing and regulation in diabetes. J Diabetes Complications 16 (2002) 72-80
37. Marshall S., Garvey W.T., and Traxinger R.R. New insights into the metabolic regulation of insulin action and insulin resistance: role of glucose and amino acids. FASEB J 5 (1991) 3031-3036
38. Baron A.D., Zhu J.S., Zhu J.H., Weldon H., Maianu L., and Garvey W.T. Glucosamine induces insulin resistance in vivo by affecting GLUT 4 translocation in skeletal muscle. Implications for glucose toxicity. J Clin Invest 96 (1995) 2792-2801
39. Kuo M., Zilberfarb V., Gangneux N., Christeff N., and Issad T. O-GlcNAc modification of FoxO1 increases its transcriptional activity: a role in the glucotoxicity phenomenon?. Biochimie 90 (2008) 679-685
40. Pouwels M.J., Tack C.J., Span P.N., Olthaar A.J., Sweep C.G., Huvers F.C., et al. Role of hexosamines in insulin resistance and nutrient sensing in human adipose and muscle tissue. J Clin Endocrinol Metab 89 (2004) 5132-5137
41. Yki-Järvinen H., Daniels M.C., Virkamäki A., Mäkimattila S., DeFronzo R.A., and McClain D. Increased glutamine:fructose-6-phosphate amidotransferase activity in skeletal muscle of patients with NIDDM. Diabetes 45 (1996) 302-307
42. Buse M.G. Hexosamines, insulin resistance, and the complications of diabetes: current status. Am J Physiol Endocrinol Metab 290 (2006) E1-E8
43. Srinivasan V., Sandhya N., Sampathkumar R., Farooq S., Mohan V., and Balasubramanyam M. Glutamine fructose-6-phosphate amidotransferase (GFAT) gene expression and activity in patients with type 2 diabetes: inter-relationships with hyperglycaemia and oxidative stress. Clin Biochem 40 (2007) 952-957
44. Wells L., Vosseller K., and Hart G.W. A role for N-acetylglucosamine as a nutrient sensor and mediator of insulin resistance. Cell Mol Life Sci 60 (2003) 222-228
45. Considine R.V. Regulation of leptin production. Rev Endocr Metab Disord 2 (2001) 357-363
46. Pouwels M.J., Jacobs J.R., Span P.N., Lutterman J.A., Smits P., and Tack C.J. Short-term glucosamine infusion does not affect insulin sensitivity in humans. J Clin Endocrinol Metab 86 (2001) 2099-2103
47. Rudich A., Kozlovsky N., Potashnik R., and Bashan N. Oxidant stress reduces insulin responsiveness in 3T3-L1 adipocytes. Am J Physiol 272 (1997) E935-E940
48. Tirosh A., Rudich A., Potashnik R., and Bashan N. Oxidative stress impairs insulin but not platelet-derived growth factor signalling in 3T3-L1 adipocytes. Biochem J 355 (2001) 757-763
49. Robertson R.P., and Harmon J.S. Diabetes, glucose toxicity, and oxidative stress: a case of double jeopardy for the pancreatic islet beta cell. Free Radic Biol Med 41 2 (2006 Jul 15) 177-184
50. Rolo A.P., and Palmeira C.M. Diabetes and mitochondrial function: role of hyperglycemia and oxidative stress. Toxicol Appl Pharmacol 212 (2006) 167-178
51. Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 414 (2001) 813-820
52. Tanaka Y., Gleason C.E., Tran P.O., Harmon J.S., and Robertson R.P. Prevention of glucose toxicity in HIT-T15 cells and Zucker diabetic fatty rats by antioxidants. Proc Natl Acad Sci U S A 96 (1999) 10857-10862
53. Kaneto H., Kajimoto Y., Miyagawa J., Matsuoka T., Fujitani Y., Umayahara Y., et al. Beneficial effects of antioxidants in diabetes: possible protection of pancreaticbeta-cells against glucose toxicity. Diabetes 48 (1999) 2398-2406
54. Sauerhöfer S., Yuan G., Braun G.S., Deinzer M., Neumaier M., Gretz N., et al. L-carnosine, a substrate of carnosinase-1, influences glucose metabolism. Diabetes 56 (2007) 2425-2432
55. Grankvist K., Marklund S.L., and Täljedal I.B. CuZn-superoxide dismutase, Mn-superoxide dismutase, catalase and glutathione peroxidase in pancreatic islets and other tissues in the mouse. Biochem J 199 (1981) 393-398
56. Maassen J.A., 'T Hart L.M., Van Essen E., Heine R.J., Nijpels G., Jahangir Tafrechi R.S., et al. Mitochondrial diabetes: molecular mechanisms and clinical presentation. Diabetes 53 (2004) S103-S109
57. Lamson D.W., and Plaza S.M. Mitochondrial factors in the pathogenesis of diabetes: a hypothesis for treatment. Altern Med Rev 7 (2002) 94-111
58. Serradas P., Giroix M.H., Saulnier C., Gangnerau M.N., Borg L.A., Welsh M., et al. Mitochondrial deoxyribonucleic acid content is specifically decreased in adult, but not fetal, pancreatic islets of the Goto-Kakizaki rat, a genetic model of noninsulin-dependent diabetes. Endocrinology 136 (1995) 5623-5631
59. Lee H.K., Song J.H., Shin C.S., Park D.J., Park K.S., Lee K.U., et al. Decreased mitochondrial DNA content in peripheral blood precedes the development of non-insulin-dependent diabetes mellitus. Diabetes Res Clin Pract 42 (1998) 161-167
60. Evans J.L., Maddux B.A., and Goldfine I.D. The molecular basis for oxidative stress-induced insulin resistance. Antioxid Redox Signal 7 (2005) 1040-1052
61. Bloch-Damti A., and Bashan N. Proposed mechanism for the induction of insulin resistance by oxidative stress. Antioxid Redox Signal 7 (2005) 1553-1567
62. International Prandial Glucose Regulation Study Group. Postprandial hyperglycaemia and cardiovascular complications of diabetes: an update. Nutr Metab Cardiovasc Dis 16 (2006) 453-456
63. Ceriello A., Colagiuri S., Gerich J., and Tuomilehto J. Guideline Development Group. Guideline for management of postmeal glucose. Nutr Metab Cardiovasc Dis 18 (2008) S17-S33
64. Monnier L., Mas E., Ginet C., Michel F., Villon L., Cristol J.P., et al. Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA 295 (2006) 1681-1687
65. Erlinger T.P., and Brancati F.L. Postchallenge hyperglicemia in a National sample of U.S. adults with type 2 diabetes. Diabetes Care 24 (2001) 1734-1738
66. Bonora E., Corrao G., Bagnardi V., Ceriello A., Comaschi M., Montanari P., et al. Prevalence and correlates of postprandial hyperglicemia in a large sample of patients with type 2 diabetes mellitus. Diabetologia 49 (2006) 846-854
67. Hanefeld M., Fischer S., Julius U., Schulze J., Schwanebeck U., Schmechel H., et al. Risk factors for miocardial infarction and death in newly detected NIDDM: the Diabetes Intervention Study, 11 year of follow up. Diabetologia 39 (1996) 1577-1583
68. Marfella R., Quagliaro L., Nappo F., Ceriello A., and Giugliano D. Acute hyperglicemia induce an oxidative stress in healthy subjects. J Clin Invest 108 (2001) 635-636
69. Meugnier E., Faray M., Rome S., Beauregard G., Michaut A., Pelloux V., et al. Acute hyperglycemia induces a global downregulation of gene expression in adipose tissue and skeletal muscle of healthy subjects. Diabetes 56 (2007) 992-999
70. Chen K.S., Heydrick S.J., Brown M.L., Friel J.C., and Ruderman N.B. Insulin increases a biochemically distinct pool of diacylglycerol in the rat soleus muscle. Am J Physiol 266 (1994) E479-E485
71. Moscat J., Diaz-Meco M.T., and Rennert P. NF-kappaB activation by protein kinase C isoforms and B-cell function. EMBO Rep 4 (2003) 31-36
72. Avogaro A., Fadini G.P., Gallo A., Pagnin E., and de Kreutzenberg S. Endothelial dysfunction in type 2 diabetes mellitus. Nutr Metab Cardiovasc Dis 16 (2006) S39-S45
73. Freidenberg G.R., Henry R.R., Klein H.H., Reichart D.R., and Olefsky J.M. Decreased kinase activity of insulin receptors from adipocytes of non-insulin-dependent diabetic subjects. J Clin Invest 79 (1987) 240-250
74. Freidenberg G.R., Reichart D., Olefsky J.M., and Henry R.R. Reversibility of defective adipocyte insulin receptor kinase activity in non-insulin-dependent diabetes mellitus. Effect of weight loss. J Clin Invest 82 (1988) 1398-1406
75. Maegawa H., Shigeta Y., Egawa K., and Kobayashi M. Impaired autophosphorylation of insulin receptors from abdominal skeletal muscles in nonobese subjects with NIDDM. Diabetes 40 (1991) 815-819
76. Obermaier-Kusser B., White M.F., Pongratz D.E., Su Z., Ermel B., Muhlbacher C., et al. A defective intramolecular autoactivation cascade may cause the reduced kinase activity of the skeletal muscle insulin receptor from patients with non-insulin-dependent diabetes mellitus. J Biol Chem 264 (1989) 9497-9504
77. Häring H.U., Tippmer S., Kellerer M., Mosthaf L., Kroder G., Bossenmaier B., et al. Modulation of insulin receptor signaling. Potential mechanisms of a cross talk between bradykinin and the insulin receptor. Diabetes 45 (1996) S115-S119
78. Müller H.K., Kellerer M., Ermel B., Mühlhöfer A., Obermaier-Kusser B., Vogt B., et al. Prevention by protein kinase C inhibitors of glucose-induced insulin-receptor tyrosine kinase resistance in rat fat cells. Diabetes 40 (1991) 1440-1448
79. Berti L., Mosthaf L., Kroder G., Kellerer M., Tippmer S., Mushack J., et al. Glucose-induced translocation of protein kinase C isoforms in rat-1 fibroblasts is paralleled by inhibition of the insulin receptor tyrosine kinase. J Biol Chem 269 (1994) 3381-3386
80. Schram M.T., Chaturvedi N., Schalkwijk C., Giorgino F., Ebeling P., Fuller J.H., et al. EURODIAB Prospective Complications Study. Vascular risk factors and markers of endothelial function as determinants of inflammatory markers in type 1 diabetes: the EURODIAB Prospective Complications Study. Diabetes Care 26 (2003) 2165-2173
81. Schalkwijk C.G., Poland D.C., van Dijk W., Kok A., Emeis J.J., Dräger A.M., et al. Plasma concentration of C-reactive protein is increased in type I diabetic patients without clinical macroangiopathy and correlates with markers of endothelial dysfunction: evidence for chronic inflammation. Diabetologia 42 (1999) 351-357
82. Devaraj S., Glaser N., Griffen S., Wang-Polagruto J., Miguelino E., and Jialal I. Increased monocytic activity and biomarkers of inflammation in patients with type 1 diabetes. Diabetes 55 (2006) 774-779
83. Dasu M.R., Devaraj S., Zhao L., Hwang D.H., and Jialal I. High glucose induces toll-like receptor expression in human monocytes: mechanism of activation. Diabetes 57 (2008) 3090-3098
84. Mandrup-Poulsen T. The role of interleukin-1 in the pathogenesis of IDDM. Diabetologia 39 (1996) 1005-1029
85. Maedler K., Sergeev P., Ris F., Oberholzer J., Joller-Jemelka H.I., Spinas G.A., et al. Glucose-induced beta cell production of IL-1beta contributes to glucotoxicity in human pancreatic islets. J Clin Invest 110 (2002) 851-860
86. Stassi G., De Maria R., Trucco G., Rudert W., Testi R., Galluzzo A., et al. Nitric oxide primes pancreatic beta cells for Fas-mediated destruction in insulin-dependent diabetes mellitus. J Exp Med 186 (1997) 1193-1200
87. Beutler B. Inferences, questions and possibilities in Toll-like receptor signalling. Nature 430 (2004) 257-263
88. Yki-Jarvinen H., and Koivisto V.A. Natural course of insulin resistance in type I diabetes. N Engl J Med 315 (1986) 224-230
89. Lillioja S., Mott D.M., Howard B.V., Bennett P.H., 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 318 (1988) 1217-1225
90. Sakul H., Pratley R., Cardon L., Ravussin E., Mott D., and Bogardus C. Familiarity of physical and metabolic characteristics that predict the development of non-insulin-dependent diabetes mellitus in Pima Indians. Am J Hum Genet 60 (1997) 651-656
91. Yki-Jarvinen H., Helve E., and Koivisto V.A. Hyperglycemia decreases glucose uptake in type I diabetes. Diabetes 36 (1987) 892-896
92. Vuorinen-Markkola H., Koivisto V.A., and Yki-Jarvinen H. Mechanisms of hyperglycemia-induced insulin resistance in whole body and skeletal muscle of type I diabetic patients. Diabetes 41 (1992) 571-580
93. U.K. prospective diabetes study 16. Overview of 6 years' therapy of type II diabetes: a progressive disease. U.K. Prospective Diabetes Study Group Diabetes 1995;44:1249-1258.
94. Marchetti P., Del Prato S., Lupi R., and Del Guerra S. The pancreatic beta-cell in human Type 2 diabetes. Nutr Metab Cardiovasc Dis 16 Suppl 1 (2006) S3-S6
95. Butler A.E., Janson J., Bonner Weir S., Ritzel R., Rizza R.A., and Butler P.C. Beta cell deficit and increased beta cell apoptosis in humans with type 2 diabetes. Diabetes 52 (2003) 102-110
96. Ilkova H., Glaser B., Tunckale A., Bagriacik N., and Cerasi E. Induction of long term glycemic control in newly diagnosed type 2 diabetic patients by transient insulin intensive treatment. Diabetes Care 20 (1997) 1353-1356
97. Weng J., Li Y., Xu W., Shi L., Zhang Q., Zhu D., et al. Effect of intensive insulin therapy on beta-cell function and glycaemic control in patients with newly diagnosed type 2 diabetes: a multicentre randomised parallel-group trial. Lancet 371 (2008) 1753-1760
98. Del Guerra S., Grupillo M., Masini M., Lupi R., Bugliani M., Torri S., et al. Gliclazide protects human islet beta-cells from apoptosis induced by intermittent high glucose Diabetes Metab Res Rev 23 (2007) 234-238
99. Musi N., and Goodyear L.J. Insulin resistance and improvements in signal transduction. Endocrine 29 (2006) 73-80
100. 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 89 (2004) 5535-5541
101. Zeender E., Maedler K., Bosco D., Berney T., Donath M.Y., and Halban P.A. Pioglitazone and sodium salicylate protect human beta cells against apoptosis and impaired function induced by glucose and interleukin 1 beta. J Clin Endocrinol Metab 89 (2004) 5059-5066
102. Chiasson J.L., Josse R.G., Gomis R., Hanefeld M., Karasik A., and Laakso M. STOP-NIDDM Trial Research Group. Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM trial. JAMA 290 (2003) 486-494
103. Holst J.J., and Orskov C. The incretin approach for diabetes treatment modulation of if islet hormone release by GLP 1 agonism. Diabetes 53 (2004) S197-S204
104. Farilla L., Hui H., Bertolotto C., Kang E., Bullotta A., Di Mario U., et al. Glucagon-like peptide 1 promotes islet cell growth and inhibits apoptosis in Zucker diabetic rats. Endocrinology 143 (2002) 4397-4408
105. Kahn S.E., Haffner S.M., Heise M.A., Herman W.H., Holman R.R., Jones N.P., et al. For the ADOPT Study group. Glycemic durability of rosiglitazone, metformin of glyburide monotherapy. N Engl J Med 355 (2006) 2427-2443
106. Uusitupa M.I., Niskanen L.K., Sitonen O., Voutilanein E., and Pyorala K. Ten year cardiovascular mortality in relation to risk factors and abnormalities in lipoprotein composition in type 2 diabetic and non diabetic subjects. Diabetologia 36 (1993) 1175-1184
107. Lehto S., Ronnemaa T., Haffner S.M., Pyorala K., Kallio V., and Laakso M. Dyslipidemia and hyperglycemia predict coronary heart disease events in middle aged patients with NIDDM. Diabetes 46 (1997) 1354-1359
108. Lehto S., Ronnemaa T., Haffner S.M., Pyorala K., Kallio V., and Laakso M. Predictors of stroke in middle aged patients with non insulin dependent diabetes. Stroke 27 (1996) 63-68
109. Standl E., Balletshofer B., Dahl B., Weichenain B., Stiegler H., Hormann A., et al. R Predictors of 10 year macrovascular and overall mortality in patients with NIDDM: the Munich General Practitioner Project. Diabetologia 39 (1996) 1540-1545
110. UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes. Lancet 352 (1998) 854-865
111. Nathan D.M., Cleary P.A., Backlund J.Y., Genuth S.M., Lachin J.M., Orchard T.J., et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med 353 (2005) 2643-2653
112. The Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 358 (2008) 2545-2559
113. The ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 358 (2005) 2560-2572
114. Duckworth W., Abraira C., Moritz T., Reda D., Emanuele N., Reaven P.D., et al. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med 360 (2005) 129-139
115. Holman R.R., Paul S.K., Bethel M.A., Matthews D.R., and Neil H.A. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 359 (2008) 1577-1589
116. Klein R. Hyperglycemia and microvascular and macrovascular disease in diabetes. Diabetes Care 18 (1995) 258-268
117. American Diabetes Association. Position statement: diagnosis and classification of diabetes mellitus. Diabetes Care 32 (2009) S62-S67
118. Lachin J.M., Genuth S., Nathan D.M., Zinman B., Rutledge B.N., and DCCT/EDIC Research Group. Effect of glycemic exposure on the risk of microvascular complications in the diabetes control and complications trial-revisited. Diabetes 57 (2008) 995-1001
119. Diabetes Control and Complications Trial Research Group. Progression of retinopathy with intensive versus conventional treatment in the Diabetes Control and Complications Trial. Ophthalmology 102 (1995) 647-661
120. Clarke M., and Dodson P.M. PKC inhibition and diabetic microvascular complications. Best Pract Res Clin Endocrinol Metab 21 (2007) 573-586
121. Noh H., and King G.L. The role of protein kinase C activation in diabetic nephropathy. Kidney Int Suppl 106 (2007) S49-S53
122. Raptis A.E., and Viberti G. Pathogenesis of diabetic nephropathy. Exp Clin Endocrinol Diabetes 109 (2001) S424-S437
123. Pugliese G. Do advanced glycation end products contribute to the development of long-term diabetic complications?. Nutr Metab Cardiovasc Dis 18 (2008) 457-460
124. DREAM (Diabetes REduction Assessment with ramipril and rosiglitazone Medication) Trial Investigators. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet 368 (2006) 1096-1105
125. Rendell M. The role of sulphonylureas in the management of type 2 diabetes mellitus. Drugs 64 (2004) 1339-1358
126. Mannucci E., and Rotella C.M. Future perspectives on glucagon-like peptide-1, diabetes and cardiovascular risk. Nutr Metab Cardiovasc Dis 18 (2008) 639-645
127. Holst J.J. Glucagon-like peptide-1: from extract to agent. The Claude Bernard Lecture, 2005. Diabetologia 49 (2006) 253-260
128. Fujimori Y., Katsuno K., Nakashima I., Ishikawa-Takemura Y., Fujikura H., and Isaji M. Remogliflozin etabonate, in a novel category of selective low-affinity sodium glucose cotransporter (SGLT2) inhibitors, exhibits antidiabetic efficacy in rodent models. J Pharmacol Exp Ther 327 (2008) 268-276
129. Meng W., Ellsworth B.A., Nirschl A.A., McCann P.J., Patel M., Girotra R.N., et al. Discovery of dapagliflozin: a potent, selective renal sodium-dependent glucose cotransporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes. J Med Chem 51 (2008) 1145-1149
130. Katsuno K., Fujimori Y., Takemura Y., Hiratochi M., Itoh F., Komatsu Y., et al. Sergliflozin, a novel selective inhibitor of low-affinity sodium glucose cotransporter (SGLT2), validates the critical role of SGLT2 in renal glucose reabsorption and modulates plasma glucose level. J Pharmacol Exp Ther 320 (2007) 323-330