Oxidative Stress and Stress-Activated Signaling Pathways: A Unifying Hypothesis of Type 2 Diabetes
Tóm tắt
In both type 1 and type 2 diabetes, the late diabetic complications in nerve, vascular endothelium, and kidney arise from chronic elevations of glucose and possibly other metabolites including free fatty acids (FFA). Recent evidence suggests that common stress-activated signaling pathways such as nuclear factor-κB, p38 MAPK, and NH2-terminal Jun kinases/stress-activated protein kinases underlie the development of these late diabetic complications. In addition, in type 2 diabetes, there is evidence that the activation of these same stress pathways by glucose and possibly FFA leads to both insulin resistance and impaired insulin secretion. Thus, we propose a unifying hypothesis whereby hyperglycemia and FFA-induced activation of the nuclear factor-κB, p38 MAPK, and NH2-terminal Jun kinases/stress-activated protein kinases stress pathways, along with the activation of the advanced glycosylation end-products/receptor for advanced glycosylation end-products, protein kinase C, and sorbitol stress pathways, plays a key role in causing late complications in type 1 and type 2 diabetes, along with insulin resistance and impaired insulin secretion in type 2 diabetes. Studies with antioxidants such as vitamin E, α-lipoic acid, and N-acetylcysteine suggest that new strategies may become available to treat these conditions.
Từ khóa
Tài liệu tham khảo
DeFronzo, 1997, Pathogenesis of type 2 diabetes: metabolic and molecular implications for identifying diabetes genes., Diabetes Rev, 5, 177
Reaven, 2000, 604
Kahn, 1994, Insulin action, diabetogenes, and the cause of type II diabetes., Diabetes, 43, 1066, 10.2337/diab.43.8.1066
Porte Jr, 2001, Clinical importance of insulin secretion and its interaction with insulin resistance in the treatment of type 2 diabetes mellitus and its complications., Diabetes Metab Res Rev, 17, 181, 10.1002/1520-7560(200105/06)17:3<181::AID-DMRR197>3.0.CO;2-1
Grodsky, 2000, 2
Froguel, 2001, Genetic determinants of type 2 diabetes., Recent Prog Horm Res, 56, 91, 10.1210/rp.56.1.91
Kahn, 1996, Genetics of non-insulin-dependent (type-II) diabetes mellitus., Annu Rev Med, 47, 509, 10.1146/annurev.med.47.1.509
Taylor, 2000, 681
Bogardus, 1989, Distribution of in vivo insulin action in Pima Indians as mixture of three normal distributions., Diabetes, 38, 1423, 10.2337/diab.38.11.1423
Hollenbeck, 1987, Variations in insulin-stimulated glucose uptake in healthy individuals with normal glucose tolerance., J Clin Endocrinol Metab, 64, 1169, 10.1210/jcem-64-6-1169
Reaven, 1993, Insulin resistance and insulin secretion are determinants of oral glucose tolerance in normal individuals., Diabetes, 42, 1324, 10.2337/diab.42.9.1324
Reaven, 1989, Relationship between glucose tolerance, insulin secretion, and insulin action in non-obese individuals with varying degrees of glucose tolerance., Diabetologia, 32, 52, 10.1007/BF00265404
Brownlee, 2001, Biochemistry and molecular cell biology of diabetic complications., Nature, 414, 813, 10.1038/414813a
Brownlee, 1981, The biochemistry of the complications of diabetes mellitus., Annu Rev Biochem, 50, 385, 10.1146/annurev.bi.50.070181.002125
Brownlee, 2000, Negative consequences of glycation., Metabolism, 49, 9, 10.1016/S0026-0495(00)80078-5
Wolff, 1987, Glucose autoxidation and protein modification. The potential role of ‘autoxidative glycosylation’ in diabetes., Biochem J, 245, 243, 10.1042/bj2450243
Wolff, 1991, Protein glycation and oxidative stress in diabetes mellitus and ageing., Free Radic Biol Med, 10, 339, 10.1016/0891-5849(91)90040-A
Wojtczak, 1993, Effect of fatty acids on energy coupling processes in mitochondria., Biochim Biophys Acta, 1183, 41, 10.1016/0005-2728(93)90004-Y
Carlsson, 1999, Sodium palmitate induces partial mitochondrial uncoupling and reactive oxygen species in rat pancreatic islets in vitro., Endocrinology, 140, 3422, 10.1210/endo.140.8.6908
Yamagishi, 2001, Leptin induces mitochondrial superoxide production and monocyte chemoattractant protein-1 expression in aortic endothelial cells by increasing fatty acid oxidation via protein kinase A., J Biol Chem, 276, 25096, 10.1074/jbc.M007383200
Rao, 2001, Peroxisomal β-oxidation and steatohepatitis., Semin Liver Dis, 21, 43, 10.1055/s-2001-12928
Reaven, 1988, Role of insulin resistance in human disease., Diabetes, 37, 1595, 10.2337/diab.37.12.1595
Reaven, 1993, Role of insulin resistance in human disease (syndrome X): an expanded definition., Annu Rev Med, 44, 121, 10.1146/annurev.me.44.020193.001005
1993, The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus., N Engl J Med, 329, 977, 10.1056/NEJM199309303291401
1998, Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33)., Lancet, 352, 837, 10.1016/S0140-6736(98)07019-6
Turner, 1998, Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34)., Lancet, 352, 854, 10.1016/S0140-6736(98)07037-8
King, 1996, The cellular and molecular mechanisms of diabetic complications., Endocrinol Metab Clin North Am, 25, 255, 10.1016/S0889-8529(05)70324-8
Fenner, 1997, Vascular dysfunction in diabetes mellitus, Lancet, 350, 9, 10.1016/S0140-6736(97)90022-2
Halliwell, 1993, The role of oxygen radicals in human disease, with particular reference to the vascular system, Haemostasis, 23, 118
Rosen, 2001, The role of oxidative stress in the onset and progression of diabetes and its complications: a summary of a Congress Series sponsored by UNESCO-MCBN, the American Diabetes Association, and the German Diabetes Society., Diabetes Metab Res Rev, 17, 189, 10.1002/dmrr.196
Greene, 1987, Sorbitol, phosphoinositides, and sodium-potassium-ATPase in the pathogenesis of diabetic complications., N Engl J Med, 316, 599, 10.1056/NEJM198703053161007
West, 2000, Radicals and oxidative stress in diabetes., Diabet Med, 17, 171, 10.1046/j.1464-5491.2000.00259.x
Ghiselli, 1992, Salicylate hydroxylation as an early marker of in vivo oxidative stress in diabetic patients., Free Radic Biol Med, 13, 621, 10.1016/0891-5849(92)90036-G
Giugliano, 1995, Diabetes mellitus, hypertension, and cardiovascular disease: which role for oxidative stress?, Metabolism, 44, 363, 10.1016/0026-0495(95)90167-1
Maxwell, 1997, Antioxidant status in patients with uncomplicated insulin-dependent and non-insulin-dependent diabetes mellitus., Eur J Clin Invest, 27, 484, 10.1046/j.1365-2362.1997.1390687.x
Baynes, 1996, The role of oxidative stress in diabetic complications., Curr Opin Endocrinol, 3, 277, 10.1097/00060793-199608000-00001
Nourooz-Zadeh, 1995, Elevated levels of authentic plasma hydroperoxides in NIDDM., Diabetes, 44, 1054, 10.2337/diab.44.9.1054
Nourooz-Zadeh, 1997, Relationships between plasma measures of oxidative stress and metabolic control in NIDDM., Diabetologia, 40, 647, 10.1007/s001250050729
Sundaram, 1996, Antioxidant status and lipid peroxidation in type II diabetes mellitus with and without complications., Clin Sci (Colch), 90, 255, 10.1042/cs0900255
Tesfamariam, 1994, Free radicals in diabetic endothelial cell dysfunction., Free Radic Biol Med, 16, 383, 10.1016/0891-5849(94)90040-X
Vlassara, 1994, Advanced glycation end products induce glomerular sclerosis and albuminuria in normal rats., Proc Natl Acad Sci USA, 91, 11704, 10.1073/pnas.91.24.11704
Culotta, 2000, Superoxide dismutase, oxidative stress, and cell metabolism., Curr Top Cell Regul, 36, 117, 10.1016/S0070-2137(01)80005-4
Hartnett, 2000, Serum markers for oxidative stress and severity of diabetic retinopathy., Diabetes Care, 23, 234, 10.2337/diacare.23.2.234
Uchimura, 1999, Changes in superoxide dismutase activities and concentrations and myeloperoxidase activities in leukocytes from patients with diabetes mellitus., J Diabetes Complications, 13, 264, 10.1016/S1056-8727(99)00053-7
Salonen, 1995, Increased risk of non-insulin dependent diabetes mellitus at low plasma vitamin E concentrations: a four year follow up study in men., BMJ, 311, 1124, 10.1136/bmj.311.7013.1124
Opara, 1999, Depletion of total antioxidant capacity in type 2 diabetes., Metabolism, 48, 1414, 10.1016/S0026-0495(99)90152-X
Shigeta, 1961, Study on the serum level of thioctic acid in patients with various diseases., J Vitaminol (Kyoto), 7, 48, 10.5925/jnsv1954.7.48
Góth, 2001, Blood catalase deficiency and diabetes in Hungary., Diabetes Care, 24, 1839, 10.2337/diacare.24.10.1839
Góth, 2000, Hereditary catalase deficiencies and increased risk of diabetes., Lancet, 356, 1820, 10.1016/S0140-6736(00)03238-4
Nishikawa, 2000, The missing link: a single unifying mechanism for diabetic complications., Kidney Int, 58, 26, 10.1046/j.1523-1755.2000.07705.x
Koya, 1998, Protein kinase C activation and the development of diabetic complications., Diabetes, 47, 859, 10.2337/diabetes.47.6.859
Nadler, 2000, 1008
Bursell, 1999, High-dose vitamin E supplementation normalizes retinal blood flow and creatinine clearance in patients with type 1 diabetes., Diabetes Care, 22, 1245, 10.2337/diacare.22.8.1245
Ishii, 1996, Amelioration of vascular dysfunctions in diabetic rats by an oral PKC-β inhibitor., Science, 272, 728, 10.1126/science.272.5262.728
Ziegler, 1999, α-Lipoic acid in the treatment of diabetic polyneuropathy in Germany: current evidence from clinical trials., Exp Clin Endocrinol Diabetes, 107, 421, 10.1055/s-0029-1212132
Jacot, 1999, Emerging therapeutics for diabetic retinopathy: potential therapies for the new millennium., Emerg Therap Targets, 3, 307, 10.1517/14728222.3.2.307
Ziegler, 1995, Treatment of symptomatic diabetic peripheral neuropathy with the anti-oxidant α-lipoic acid. A 3-week multicentre randomized controlled trial (ALADIN Study)., Diabetologia, 38, 1425, 10.1007/BF00400603
Mohamed, 1999, The role of oxidative stress and NF-κB activation in late diabetic complications., Biofactors, 10, 157, 10.1002/biof.5520100211
Stehouwer, 1996, The pathogenesis of vascular complications of diabetes mellitus: one voice or many?, Eur J Clin Invest, 26, 535, 10.1046/j.1365-2362.1996.1780527.x
Yaqoob, 1993, Relationship between markers of endothelial dysfunction, oxidant injury and tubular damage in patients with insulin-dependent diabetes mellitus., Clin Sci (Colch), 85, 557, 10.1042/cs0850557
Nishikawa, 2000, Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage., Nature, 404, 787, 10.1038/35008121
Boveris, 1984, Determination of the production of superoxide radicals and hydrogen peroxide in mitochondria., Methods Enzymol, 105, 429, 10.1016/S0076-6879(84)05060-6
Chance, 1979, Hydroperoxide metabolism in mammalian organs., Physiol Rev, 59, 527, 10.1152/physrev.1979.59.3.527
Hansford, 1997, Dependence of H2O2 formation by rat heart mitochondria on substrate availability and donor age., J Bioenerg Biomembr, 29, 89, 10.1023/A:1022420007908
Turrens, 1980, Generation of superoxide anion by the NADH dehydrogenase of bovine heart mitochondria., Biochem J, 191, 421, 10.1042/bj1910421
Shigenaga, 1994, Oxidative damage and mitochondrial decay in aging., Proc Natl Acad Sci USA, 91, 10771, 10.1073/pnas.91.23.10771
Cadenas, 2000, Mitochondrial free radical generation, oxidative stress, and aging., Free Radic Biol Med, 29, 222, 10.1016/S0891-5849(00)00317-8
Boveris, 1977, Mitochondrial production of superoxide radical and hydrogen peroxide., Adv Exp Med Biol, 78, 67, 10.1007/978-1-4615-9035-4_5
Melov, 1999, Mitochondrial disease in superoxide dismutase 2 mutant mice., Proc Natl Acad Sci USA, 96, 846, 10.1073/pnas.96.3.846
Melov, 2000, Mitochondrial oxidative stress. Physiologic consequences and potential for a role in aging., Ann NY Acad Sci, 908, 219, 10.1111/j.1749-6632.2000.tb06649.x
Lu, 2000, Regulation of glutathione synthesis., Curr Top Cell Regul, 36, 95, 10.1016/S0070-2137(01)80004-2
Biewenga, 1997, The pharmacology of the antioxidant lipoic acid., Gen Pharmacol, 29, 315, 10.1016/S0306-3623(96)00474-0
Packer, 1995, α-Lipoic acid as a biological antioxidant., Free Radic Biol Med, 19, 227, 10.1016/0891-5849(95)00017-R
Dröge, 2002, Free radicals in the physiological control of cell function., Physiol Rev, 82, 47, 10.1152/physrev.00018.2001
Dalton, 1999, Regulation of gene expression by reactive oxygen., Annu Rev Pharmacol Toxicol, 39, 67, 10.1146/annurev.pharmtox.39.1.67
Allen, 2000, Oxidative stress and gene regulation., Free Radic Biol Med, 28, 463, 10.1016/S0891-5849(99)00242-7
Mercurio, 1999, NF-κB as a primary regulator of the stress response., Oncogene, 18, 6163, 10.1038/sj.onc.1203174
Barnes, 1997, Nuclear factor-κB: a pivotal transcription factor in chronic inflammatory diseases., N Engl J Med, 336, 1066, 10.1056/NEJM199704103361506
Baldwin Jr, 2001, The transcription factor NF-κB and human disease., J Clin Invest, 107, 3, 10.1172/JCI11891
Karin, 2000, Phosphorylation meets ubiquitination: the control of NF-κB activity., Annu Rev Immunol, 18, 621, 10.1146/annurev.immunol.18.1.621
Karin, 1999, How NF-κB is activated: the role of the IκB kinase (IKK) complex., Oncogene, 18, 6867, 10.1038/sj.onc.1203219
DiDonato, 1997, A cytokine-responsive IκB kinase that activates the transcription factor NF-κB., Nature, 388, 548, 10.1038/41493
Mercurio, 1997, IKK-1 and IKK-2: cytokine-activated IκB kinases essential for NF-κB activation., Science, 278, 860, 10.1126/science.278.5339.860
Ling, 1998, NF-κB-inducing kinase activates IKK-α by phosphorylation of Ser-176., Proc Natl Acad Sci USA, 95, 3792, 10.1073/pnas.95.7.3792
Delhase, 1999, Positive and negative regulation of IκB kinase activity through IKKβ subunit phosphorylation., Science, 284, 309, 10.1126/science.284.5412.309
Yin, 1998, The anti-inflammatory agents aspirin and salicylate inhibit the activity of IκB kinase-β., Nature, 396, 77, 10.1038/23948
Rossi, 2000, Anti-inflammatory cyclopentenone prostaglandins are direct inhibitors of IκB kinase., Nature, 403, 103, 10.1038/47520
Straus, 2000, 15-Deoxy-Δ12,14-prostaglandin J2 inhibits multiple steps in the NF-κB signaling pathway., Proc Natl Acad Sci USA, 97, 4844, 10.1073/pnas.97.9.4844
Ricote, 1998, The peroxisome proliferator-activated receptor-γ is a negative regulator of macrophage activation., Nature, 391, 79, 10.1038/34178
Gilroy, 1999, Inducible cyclooxygenase may have anti-inflammatory properties., Nat Med, 5, 698, 10.1038/9550
Forman, 1995, 15-Deoxy-Δ(12,14)-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR γ., Cell, 83, 803, 10.1016/0092-8674(95)90193-0
Lehmann, 1995, An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor γ (PPAR-γ)., J Biol Chem, 270, 12953, 10.1074/jbc.270.22.12953
Willson, 1996, The structure-activity relationship between peroxisome proliferator-activated receptor γ agonism and the antihyperglycemic activity of thiazolidinediones., J Med Chem, 39, 665, 10.1021/jm950395a
Saltiel, 1996, Thiazolidinediones in the treatment of insulin resistance and type II diabetes., Diabetes, 45, 1661, 10.2337/diab.45.12.1661
Hofmann, 1998, Insufficient glycemic control increases nuclear factor-κB binding activity in peripheral blood mononuclear cells isolated from patients with type 1 diabetes., Diabetes Care, 21, 1310, 10.2337/diacare.21.8.1310
Hofmann, 1999, Peripheral blood mononuclear cells isolated from patients with diabetic nephropathy show increased activation of the oxidative-stress sensitive transcription factor NF-κB., Diabetologia, 42, 222, 10.1007/s001250051142
Godin, 1988, Antioxidant enzyme alterations in experimental and clinical diabetes., Mol Cell Biochem, 84, 223, 10.1007/BF00421057
Bursell, 1999, Can protein kinase C inhibition and vitamin E prevent the development of diabetic vascular complications?, Diabetes Res Clin Pract, 45, 169, 10.1016/S0168-8227(99)00047-9
Packer, 2000
Kleemann, 1989, 11
Jacob, 1999, Oral administration of RAC-α-lipoic acid modulates insulin sensitivity in patients with type 2 diabetes mellitus: a placebo-controlled pilot trial., Free Radic Biol Med, 27, 309, 10.1016/S0891-5849(99)00089-1
Konrad, 1999, α-Lipoic acid treatment decreases serum lactate and pyruvate concentrations and improves glucose effectiveness in lean and obese patients with type 2 diabetes., Diabetes Care, 22, 280, 10.2337/diacare.22.2.280
Evans, 2000, α-Lipoic acid: a multi-functional antioxidant that improves insulin sensitivity in patients with type 2 diabetes., Diabetes Technol Ther, 2, 401, 10.1089/15209150050194279
Han, 1997, Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization., Biofactors, 6, 321, 10.1002/biof.5520060303
Bierhaus, 1997, Advanced glycation end product-induced activation of NF-κB is suppressed by α-lipoic acid in cultured endothelial cells., Diabetes, 46, 1481, 10.2337/diab.46.9.1481
Zhang, 2001, α-Lipoic acid inhibits TNF-α-induced NF-κB activation and adhesion molecule expression in human aortic endothelial cells., FASEB J, 15, 2423, 10.1096/fj.01-0260com
Ho, 1999, Supplementation of N-acetylcysteine inhibits NFκB activation and protects against alloxan-induced diabetes in CD-1 mice., FASEB J, 13, 1845, 10.1096/fasebj.13.13.1845
Oka, 2000, N-Acetylcysteine suppresses TNF-induced NF-κB activation through inhibition of IκB kinases., FEBS Lett, 472, 196, 10.1016/S0014-5793(00)01464-2
Staal, 1990, Intracellular thiols regulate activation of nuclear factor κB and transcription of human immunodeficiency virus., Proc Natl Acad Sci USA, 87, 9943, 10.1073/pnas.87.24.9943
Sen, 1998, A positively charged α-lipoic acid analogue with increased cellular uptake and more potent immunomodulatory activity., Biochem Biophys Res Commun, 247, 223, 10.1006/bbrc.1998.8764
Iimuro, 2000, The glutathione precursor L-2-oxothiazolidine-4-carboxylic acid protects against liver injury due to chronic enteral ethanol exposure in the rat., Hepatology, 31, 391, 10.1002/hep.510310219
Manna, 2000, Resveratrol suppresses TNF-induced activation of nuclear transcription factors NF-κ B, activator protein-1, and apoptosis: potential role of reactive oxygen intermediates and lipid peroxidation., J Immunol, 164, 6509, 10.4049/jimmunol.164.12.6509
Holmes-McNary, 2000, Chemopreventive properties of trans-resveratrol are associated with inhibition of activation of the IκB kinase., Cancer Res, 60, 3477
Shi, 2000, Antioxidant properties of (-)-epicatechin-3-gallate and its inhibition of Cr(VI)-induced DNA damage and Cr(IV)- or TPA-stimulated NF-κB activation., Mol Cell Biochem, 206, 125, 10.1023/A:1007012403691
Peng, 2000, Pycnogenol inhibits tumor necrosis factor-α-induced nuclear factor κB activation and adhesion molecule expression in human vascular endothelial cells., Cell Mol Life Sci, 57, 834, 10.1007/s000180050045
Manna, 1999, Silymarin suppresses TNF-induced activation of NF-κB, c-Jun N-terminal kinase, and apoptosis., J Immunol, 163, 6800, 10.4049/jimmunol.163.12.6800
Pan, 2000, Comparative studies on the suppression of nitric oxide synthase by curcumin and its hydrogenated metabolites through down-regulation of IκB kinase and NFκB activation in macrophages., Biochem Pharmacol, 60, 1665, 10.1016/S0006-2952(00)00489-5
Altavilla, 2000, IRFI 042, a novel dual vitamin E-like antioxidant, inhibits activation of nuclear factor-κB and reduces the inflammatory response in myocardial ischemia-reperfusion injury., Cardiovasc Res, 47, 515, 10.1016/S0008-6363(00)00124-3
Floyd, 2000, Nitrone inhibition of age-associated oxidative damage., Ann NY Acad Sci, 899, 222, 10.1111/j.1749-6632.2000.tb06189.x
Carney, 1991, Reversal of age-related increase in brain protein oxidation, decrease in enzyme activity, and loss in temporal and spatial memory by chronic administration of the spin-trapping compound N-tert-butyl-α-phenylnitrone., Proc Natl Acad Sci USA, 88, 3633, 10.1073/pnas.88.9.3633
Thomas, 1996, Characterization of the radical trapping activity of a novel series of cyclic nitrone spin traps., J Biol Chem, 271, 3097, 10.1074/jbc.271.6.3097
Atamna, 2000, N-t-butyl hydroxylamine, a hydrolysis product of α-phenyl-N-t-butyl nitrone, is more potent in delaying senescence in human lung fibroblasts., J Biol Chem, 275, 6741, 10.1074/jbc.275.10.6741
Ho, 2000, α-Phenyl-tert-butylnitrone (PBN) inhibits NFκB activation offering protection against chemically induced diabetes., Free Radic Biol Med, 28, 604, 10.1016/S0891-5849(99)00271-3
Gorlach, 2001, Thrombin activates the hypoxia-inducible factor-1 signaling pathway in vascular smooth muscle cells: role of the p22(phox)-containing NADPH oxidase., Circ Res, 89, 47, 10.1161/hh1301.092678
Sasaki, 2000, Inhibition of NF κB activation by pyrrolidine dithiocarbamate prevents in vivo hypoxia/reoxygenation-mediated myocardial angiogenesis., Int J Tissue React, 22, 93
Redondo, 2000, Vascular endothelial growth factor (VEGF) and melanoma. N-acetylcysteine downregulates VEGF production in vitro., Cytokine, 12, 374, 10.1006/cyto.1999.0566
Folkman, 1995, Angiogenesis in cancer, vascular, rheumatoid and other disease., Nat Med, 1, 27, 10.1038/nm0195-27
Ferrara, 2000, Vascular endothelial growth factor and the regulation of angiogenesis., Recent Prog Horm Res, 55, 15
Yancopoulos, 2000, Vascular-specific growth factors and blood vessel formation., Nature, 407, 242, 10.1038/35025215
Aiello, 2000, Role of vascular endothelial growth factor in diabetic vascular complications, Kidney Int, 58, S113, 10.1046/j.1523-1755.2000.07718.x
Aiello, 1994, Vascular endothelial growth factor in ocular fluid of patients with diabetic retinopathy and other retinal disorders., N Engl J Med, 331, 1480, 10.1056/NEJM199412013312203
Adamis, 1994, Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy., Am J Ophthalmol, 118, 445, 10.1016/S0002-9394(14)75794-0
Miller, 1994, Vascular endothelial growth factor/vascular permeability factor is temporally and spatially correlated with ocular angiogenesis in a primate model., Am J Pathol, 145, 574
Chiarelli, 2000, Role of growth factors in the development of diabetic complications., Horm Res, 53, 53
Flyvbjerg, 2000, Putative pathophysiological role of growth factors and cytokines in experimental diabetic kidney disease., Diabetologia, 43, 1205, 10.1007/s001250051515
Chiarelli, 2000, Vascular endothelial growth factor (VEGF) in children, adolescents and young adults with type 1 diabetes mellitus: relation to glycaemic control and microvascular complications., Diabet Med, 17, 650, 10.1046/j.1464-5491.2000.00350.x
Hovind, 2000, Elevated vascular endothelial growth factor in type 1 diabetic patients with diabetic nephropathy, Kidney Int, 57, S56, 10.1046/j.1523-1755.2000.07504.x
McLaren, 1999, Elevated plasma vascular endothelial cell growth factor and thrombomodulin in juvenile diabetic patients., Clin Appl Thromb Hemost, 5, 21, 10.1177/107602969900500105
Richard, 1999, Angiogenesis: how a tumor adapts to hypoxia, Biochem Biophys Res Commun, 266, 718, 10.1006/bbrc.1999.1889
Natarajan, 1997, Effects of high glucose on vascular endothelial growth factor expression in vascular smooth muscle cells, Am J Physiol, 273, H2224
Williams, 1997, Glucose-induced protein kinase C activation regulates vascular permeability factor mRNA expression and peptide production by human vascular smooth muscle cells in vitro., Diabetes, 46, 1497, 10.2337/diab.46.9.1497
Lu, 1998, Advanced glycation end products increase retinal vascular endothelial growth factor expression., J Clin Invest, 101, 1219, 10.1172/JCI1277
Sasaki, 2000, Oxidative stress due to hypoxia/reoxygenation induces angiogenic factor VEGF in adult rat myocardium: possible role of NFκB., Toxicology, 155, 27, 10.1016/S0300-483X(00)00274-2
Chua, 1998, Upregulation of vascular endothelial growth factor by H2O2 in rat heart endothelial cells., Free Radic Biol Med, 25, 891, 10.1016/S0891-5849(98)00115-4
Kuroki, 1996, Reactive oxygen intermediates increase vascular endothelial growth factor expression in vitro and in vivo., J Clin Invest, 98, 1667, 10.1172/JCI118962
Tanaka, 2000, Induction of VEGF gene transcription by IL-1β is mediated through stress-activated MAP kinases and Sp1 sites in cardiac myocytes., J Mol Cell Cardiol, 32, 1955, 10.1006/jmcc.2000.1228
Pages, 2000, Stress-activated protein kinases (JNK and p38/HOG) are essential for vascular endothelial growth factor mRNA stability., J Biol Chem, 275, 26484, 10.1074/jbc.M002104200
Kozawa, 2000, Endothelin-1 induces vascular endothelial growth factor synthesis in osteoblasts involvement of p38 mitogen-activated protein kinase., Cell Signal, 12, 375, 10.1016/S0898-6568(00)00061-9
Chandel, 2000, Role of oxidants in NF-κB activation and TNF-α gene transcription induced by hypoxia and endotoxin., J Immunol, 165, 1013, 10.4049/jimmunol.165.2.1013
Matsushita, 2000, Hypoxia-induced endothelial apoptosis through nuclear factor-κB (NF-κB)-mediated bcl-2 suppression: in vivo evidence of the importance of NF-κB in endothelial cell regulation., Circ Res, 86, 974, 10.1161/01.RES.86.9.974
Lewis, 1998, Signal transduction through MAP kinase cascades, In: Woude GFV, Klein G, eds. Advances in cancer research. San Diego: Academic Press Inc.; vol, 74, 49
Tibbles, 1999, The stress-activated protein kinase pathways., Cell Mol Life Sci, 55, 1230, 10.1007/s000180050369
Suyama, 2001, Induction of transcription factor AP-2 by cytokines and prostaglandins in cultured mesangial cells., Am J Nephrol, 21, 307, 10.1159/000046266
Huang, 1998, Redox modulation of AP-2 DNA binding activity in vitro., Biochem Biophys Res Commun, 249, 307, 10.1006/bbrc.1998.9139
Zhu, 2001, A family of AP-2 proteins down-regulate manganese superoxide dismutase expression., J Biol Chem, 276, 14407, 10.1074/jbc.M009708200
Basu, 1998, Stress signals for apoptosis: ceramide and c-Jun kinase., Oncogene, 17, 3277, 10.1038/sj.onc.1202570
Xia, 1995, Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis., Science, 270, 1326, 10.1126/science.270.5240.1326
Park, 1996, Ordering the cell death pathway. Differential effects of BCL2, an interleukin-1-converting enzyme family protease inhibitor, and other survival agents on JNK activation in serum/nerve growth factor-deprived PC12 cells., J Biol Chem, 271, 21898, 10.1074/jbc.271.36.21898
Ho, 2000, High glucose-induced apoptosis in human endothelial cells is mediated by sequential activations of c-Jun NH(2)-terminal kinase and caspase-3., Circulation, 101, 2618, 10.1161/01.CIR.101.22.2618
Natarajan, 1999, Angiotensin II signaling in vascular smooth muscle cells under high glucose conditions., Hypertension, 33, 378, 10.1161/01.HYP.33.1.378
Bleich, 1997, The stress-activated c-Jun protein kinase (JNK) is stimulated by lipoxygenase pathway product 12-HETE in RIN m5F cells., Biochem Biophys Res Commun, 230, 448, 10.1006/bbrc.1996.5981
Makkinje, 2000, Gene 33/Mig-6, a transcriptionally inducible adapter protein that binds GTP-CDC42 and activates SAPK/JNK. A potential marker transcript for chronic pathologic conditions, such as diabetic nephropathy. Possible role in the response to persistent stress., J Biol Chem, 275, 17838, 10.1074/jbc.M909735199
Obata, 2000, MAP kinase pathways activated by stress: the p38 MAPK pathway, Crit Care Med, 28, N67, 10.1097/00003246-200004001-00008
Salituro, 1999, Inhibitors of p38 MAP kinase: therapeutic intervention in cytokine-mediated diseases., Curr Med Chem, 6, 807, 10.2174/092986730609220401150415
Lee, 2000, Inhibition of p38 MAP kinase as a therapeutic strategy., Immunopharmacology, 47, 185, 10.1016/S0162-3109(00)00206-X
Barone, 2000, Therapeutic potential of anti-inflammatory drugs in focal stroke., Expert Opin Investig Drugs, 9, 2281, 10.1517/13543784.9.10.2281
Begum, 2000, High glucose and insulin inhibit VSMC MKP-1 expression by blocking iNOS via p38 MAPK activation, Am J Physiol, 278, C81, 10.1152/ajpcell.2000.278.1.C81
Igarashi, 1999, Glucose or diabetes activates p38 mitogen-activated protein kinase via different pathways., J Clin Invest, 103, 185, 10.1172/JCI3326
Dunlop, 2000, Small heat shock protein alteration provides a mechanism to reduce mesangial cell contractility in diabetes and oxidative stress., Kidney Int, 57, 464, 10.1046/j.1523-1755.2000.00866.x
Brownlee, 1995, Advanced protein glycosylation in diabetes and aging., Annu Rev Med, 46, 223, 10.1146/annurev.med.46.1.223
Bierhaus, 1998, AGEs and their interaction with AGE-receptors in vascular disease and diabetes mellitus. I. The AGE concept., Cardiovasc Res, 37, 586, 10.1016/S0008-6363(97)00233-2
Makita, 1992, Hemoglobin-AGE: a circulating marker of advanced glycosylation., Science, 258, 651, 10.1126/science.1411574
Wolffenbuttel, 1996, Long-term assessment of glucose control by haemoglobin-AGE measurement., Lancet, 347, 513, 10.1016/S0140-6736(96)91141-1
Bierhaus, 1997, Advanced glycation end product (AGE)-mediated induction of tissue factor in cultured endothelial cells is dependent on RAGE., Circulation, 96, 2262, 10.1161/01.CIR.96.7.2262
Schmidt, 2000, RAGE: a new target for the prevention and treatment of the vascular and inflammatory complications of diabetes., Trends Endocrinol Metab, 11, 368, 10.1016/S1043-2760(00)00311-8
Esposito, 1989, Endothelial receptor-mediated binding of glucose-modified albumin is associated with increased monolayer permeability and modulation of cell surface coagulant properties., J Exp Med, 170, 1387, 10.1084/jem.170.4.1387
Li, 1997, Characterization and functional analysis of the promoter of RAGE, the receptor for advanced glycation end products., J Biol Chem, 272, 16498, 10.1074/jbc.272.26.16498
Schmidt, 1994, Cellular receptors for advanced glycation end products. Implications for induction of oxidant stress and cellular dysfunction in the pathogenesis of vascular lesions., Arterioscler Thromb, 14, 1521, 10.1161/01.ATV.14.10.1521
Ritthaler, 1995, Expression of receptors for advanced glycation end products in peripheral occlusive vascular disease., Am J Pathol, 146, 688
Yan, 1997, What’s the RAGE? The receptor for advanced glycation end products (RAGE) and the dark side of glucose., Eur J Clin Invest, 27, 179, 10.1046/j.1365-2362.1996.00072.x
Glogowski, 1999, High glucose alters the response of mesangial cell protein kinase C isoforms to endothelin-1., Kidney Int, 55, 486, 10.1046/j.1523-1755.1999.00284.x
Stevens, 2000, 972
Lee, 1999, Contributions of polyol pathway to oxidative stress in diabetic cataract., FASEB J, 13, 23, 10.1096/fasebj.13.1.23
Lee, 1995, Demonstration that polyol accumulation is responsible for diabetic cataract by the use of transgenic mice expressing the aldose reductase gene in the lens., Proc Natl Acad Sci USA, 92, 2780, 10.1073/pnas.92.7.2780
Yamaoka, 1995, Acute onset of diabetic pathological changes in transgenic mice with human aldose reductase cDNA., Diabetologia, 38, 255, 10.1007/BF00400627
Yagihashi, 1996, Galactosemic neuropathy in transgenic mice for human aldose reductase., Diabetes, 45, 56, 10.2337/diab.45.1.56
Singh, 2000, Molecular modeling of the aldose reductase-inhibitor complex based on the X-ray crystal structure and studies with single-site-directed mutants., J Med Chem, 43, 1062, 10.1021/jm990168z
Marshall, 1991, New insights into the metabolic regulation of insulin action and insulin resistance: role of glucose and amino acids., FASEB J, 5, 3031, 10.1096/fasebj.5.15.1743436
Hebert, 1996, Overexpression of glutamine:fructose-6-phosphate amidotransferase in transgenic mice leads to insulin resistance., J Clin Invest, 98, 930, 10.1172/JCI118876
Boden, 1994, Mechanisms of fatty acid-induced inhibition of glucose uptake., J Clin Invest, 93, 2438, 10.1172/JCI117252
Hawkins, 1997, Role of the glucosamine pathway in fat-induced insulin resistance., J Clin Invest, 99, 2173, 10.1172/JCI119390
Schleicher, 2000, Role of the hexosamine biosynthetic pathway in diabetic nephropathy, Kidney Int, 58, S13, 10.1046/j.1523-1755.2000.07703.x
Tang, 2000, Transgenic mice with increased hexosamine flux specifically targeted to β-cells exhibit hyperinsulinemia and peripheral insulin resistance., Diabetes, 49, 1492, 10.2337/diabetes.49.9.1492
Veerababu, 2000, 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, 2070, 10.2337/diabetes.49.12.2070
James, 2002, Flux through the hexosamine pathway is a determinant of nuclear factor κB-dependent promoter activation., Diabetes, 51, 1146, 10.2337/diabetes.51.4.1146
Wang, 1998, A nutrient-sensing pathway regulates leptin gene expression in muscle and fat., Nature, 393, 684, 10.1038/31474
Rossetti, 2000, Perspective: hexosamines and nutrient sensing., Endocrinology, 141, 1922, 10.1210/endo.141.6.7566
McClain, 2002, Hexosamines as mediators of nutrient sensing and regulation in diabetes., J Diabetes Complications, 16, 72, 10.1016/S1056-8727(01)00188-X
Du, 2000, Hyperglycemia-induced mitochondrial superoxide overproduction activates the hexosamine pathway and induces plasminogen activator inhibitor-1 expression by increasing Sp1 glycosylation., Proc Natl Acad Sci USA, 97, 12222, 10.1073/pnas.97.22.12222
Rao, 1994, Activation of mitogen-activated protein kinases by arachidonic acid and its metabolites in vascular smooth muscle cells., J Biol Chem, 269, 32586, 10.1016/S0021-9258(18)31674-0
Natarajan, 1994, Role of specific isoforms of protein kinase C in angiotensin II and lipoxygenase action in rat adrenal glomerulosa cells., Mol Cell Endocrinol, 101, 59, 10.1016/0303-7207(94)90219-4
Natarajan, 1994, Role of the lipoxygenase pathway in angiotensin II-induced vascular smooth muscle cell hypertrophy, Hypertension, 23, I142, 10.1161/01.HYP.23.1_Suppl.I142
Haliday, 1991, TNF induces c-fos via a novel pathway requiring conversion of arachidonic acid to a lipoxygenase metabolite., EMBO J, 10, 109, 10.1002/j.1460-2075.1991.tb07926.x
Laniado-Schwartzman, 1994, Activation of nuclear factor κB and oncogene expression by 12(R)-hydroxyeicosatrienoic acid, an angiogenic factor in microvessel endothelial cells., J Biol Chem, 269, 24321, 10.1016/S0021-9258(19)51085-7
Stamler, 1994, Redox signaling: nitrosylation and related target interactions of nitric oxide., Cell, 78, 931, 10.1016/0092-8674(94)90269-0
Beckman, 1990, Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide., Proc Natl Acad Sci USA, 87, 1620, 10.1073/pnas.87.4.1620
White, 1994, Superoxide and peroxynitrite in atherosclerosis., Proc Natl Acad Sci USA, 91, 1044, 10.1073/pnas.91.3.1044
Heitzer, 2001, Beneficial effects of α-lipoic acid and ascorbic acid on endothelium-dependent, nitric oxide-mediated vasodilation in diabetic patients: relation to parameters of oxidative stress., Free Radic Biol Med, 31, 53, 10.1016/S0891-5849(01)00551-2
Diaz, 1997, Antioxidants and atherosclerotic heart disease., N Engl J Med, 337, 408, 10.1056/NEJM199708073370607
Vita, 1998, l-2-Oxothiazolidine-4-carboxylic acid reverses endothelial dysfunction in patients with coronary artery disease., J Clin Invest, 101, 1408, 10.1172/JCI1155
Levine, 1996, Ascorbic acid reverses endothelial vasomotor dysfunction in patients with coronary artery disease., Circulation, 93, 1107, 10.1161/01.CIR.93.6.1107
Andrews, 2001, N-acetylcysteine improves coronary and peripheral vascular function., J Am Coll Cardiol, 37, 117, 10.1016/S0735-1097(00)01093-7
Paolisso, 1994, Evidence for a relationship between oxidative stress and insulin action in non-insulin-dependent (type II) diabetic patients., Metabolism, 43, 1426, 10.1016/0026-0495(94)90039-6
Paolisso, 1996, Oxidative stress and insulin action: is there a relationship?, Diabetologia, 39, 357, 10.1007/BF00418354
Ceriello, 2000, Oxidative stress and glycemic regulation., Metabolism, 49, 27, 10.1016/S0026-0495(00)80082-7
Wittmann, 1996, Are insulin resistance and atherosclerosis the consequences of oxidative stress?, Diabetologia, 39, 1002, 10.1007/BF00403924
Hirai, 2000, Insulin resistance and endothelial dysfunction in smokers: effects of vitamin C, Am J Physiol, 279, H1172
Hirashima, 2000, Improvement of endothelial function and insulin sensitivity with vitamin C in patients with coronary spastic angina: possible role of reactive oxygen species., J Am Coll Cardiol, 35, 1860, 10.1016/S0735-1097(00)00616-1
Caballero, 1993, Vitamin E improves the action of insulin., Nutr Rev, 51, 339, 10.1111/j.1753-4887.1993.tb03761.x
Paolisso, 1992, Plasma GSH/GSSG affects glucose homeostasis in healthy subjects and non-insulin-dependent diabetics, Am J Physiol, 263, E435
Jacob, 1995, Enhancement of glucose disposal in patients with type 2 diabetes by α-lipoic acid., Arzneimittelforschung, 45, 872
Jacob, 1996, Improvement of insulin-stimulated glucose-disposal in type 2 diabetes after repeated parenteral administration of thioctic acid., Exp Clin Endocrinol Diabetes, 104, 284, 10.1055/s-0029-1211455
Evans, 2002, Pharmacokinetics, tolerability, and fructosamine-lowering effect of a novel, controlled release formulation of α-lipoic acid., Endocr Pract, 8, 29, 10.4158/EP.8.1.29
Cohen, 1996, Dissection of protein kinase cascades that mediate cellular response to cytokines and cellular stress., Adv Pharmacol, 36, 15, 10.1016/S1054-3589(08)60574-8
Kyriakis, 1996, Sounding the alarm: protein kinase cascades activated by stress and inflammation., J Biol Chem, 271, 24313, 10.1074/jbc.271.40.24313
Adler, 1999, Role of redox potential and reactive oxygen species in stress signaling., Oncogene, 18, 6104, 10.1038/sj.onc.1203128
Paz, 1997, A molecular basis for insulin resistance. Elevated serine/threonine phosphorylation of IRS-1 and IRS-2 inhibits their binding to the juxtamembrane region of the insulin receptor and impairs their ability to undergo insulin-induced tyrosine phosphorylation., J Biol Chem, 272, 29911, 10.1074/jbc.272.47.29911
Kellerer, 1998, Protein kinase C isoforms α, δ and θ require insulin receptor substrate-1 to inhibit the tyrosine kinase activity of the insulin receptor in human kidney embryonic cells (HEK 293 cells)., Diabetologia, 41, 833, 10.1007/s001250050995
Li, 1999, Modulation of insulin receptor substrate-1 tyrosine phosphorylation by an Akt/phosphatidylinositol 3-kinase pathway., J Biol Chem, 274, 9351, 10.1074/jbc.274.14.9351
Qiao, 1999, Identification of enhanced serine kinase activity in insulin resistance., J Biol Chem, 274, 10625, 10.1074/jbc.274.15.10625
Griffin, 1999, Free fatty acid-induced insulin resistance is associated with activation of protein kinase Cθ and alterations in the insulin signaling cascade., Diabetes, 48, 1270, 10.2337/diabetes.48.6.1270
Aguirre, 2000, The c-jun NH(2)-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser(307)., J Biol Chem, 275, 9047, 10.1074/jbc.275.12.9047
Paz, 1996, Interaction between the insulin receptor and its downstream effectors. Use of individually expressed receptor domains for structure function analysis., J Biol Chem, 271, 6998, 10.1074/jbc.271.12.6998
Zick, 2001, Insulin resistance: a phosphorylation-based uncoupling of insulin signaling., Trends Cell Biol, 11, 437, 10.1016/S0962-8924(01)02129-8
Sykiotis, 2001, Serine phosphorylation of insulin receptor substrate-1: a novel target for the reversal of insulin resistance., Mol Endocrinol, 15, 1864
Rudich, 1997, Oxidant stress reduces insulin responsiveness in 3T3–L1 adipocytes, Am J Physiol, 35, E935
Rudich, 1999, Lipoic acid protects against oxidative stress induced impairment in insulin stimulation of protein kinase B and glucose transport in 3T3–L1 adipocytes., Diabetologia, 42, 949, 10.1007/s001250051253
Tirosh, 1999, Oxidative stress disrupts insulin-induced cellular redistribution of insulin receptor substrate-1 and phosphatidylinositol 3-kinase in 3T3–L1 adipocytes. A putative cellular mechanism for impaired protein kinase B activation and GLUT4 translocation., J Biol Chem, 274, 10595, 10.1074/jbc.274.15.10595
Tirosh, 2001, Oxidative stress impairs insulin but not platelet-derived growth factor signalling in 3T3–L1 adipocytes., Biochem J, 355, 757, 10.1042/bj3550757
Robinson, 1993, Glucose transport in L6 myoblasts overexpressing GLUT1 and GLUT4., J Biol Chem, 268, 22119, 10.1016/S0021-9258(20)80656-5
Maddux, 2001, Protection against oxidative stress-induced insulin resistance in rat L6 muscle cells by micromolar concentrations of α-lipoic acid., Diabetes, 50, 404, 10.2337/diabetes.50.2.404
Najib, 2001, Homocysteine thiolactone inhibits insulin signaling, and glutathione has a protective effect., J Mol Endocrinol, 27, 85, 10.1677/jme.0.0270085
Blair, 1999, Regulation of glucose transport and glycogen synthesis in L6 muscle cells during oxidative stress. Evidence for cross-talk between the insulin and SAPK2/p38 mitogen-activated protein kinase signaling pathways., J Biol Chem, 274, 36293, 10.1074/jbc.274.51.36293
Sweeney, 1999, An inhibitor of p38 mitogen-activated protein kinase prevents insulin-stimulated glucose transport but not glucose transporter translocation in 3T3–L1 adipocytes and L6 myotubes., J Biol Chem, 274, 10071, 10.1074/jbc.274.15.10071
Konrad, 2001, The antihyperglycemic drug α-lipoic acid stimulates glucose uptake via both GLUT4 translocation and GLUT4 activation: potential role of p38 mitogen-activated protein kinase in GLUT4 activation., Diabetes, 50, 1464, 10.2337/diabetes.50.6.1464
Aguirre, 2002, Phosphorylation of ser307 in insulin receptor substrate-1 blocks interactions with the insulin receptor and inhibits insulin action., J Biol Chem, 277, 1531, 10.1074/jbc.M101521200
Yuan, 2000, Salicylate inhibition of IKKβ (IκB kinase) reverses insulin resistance in Zucker (fa/fa) rats, Diabetes, 49, A292
Yuan, 2001, Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of IKKβ., Science, 293, 1673, 10.1126/science.1061620
Kim, 2001, Prevention of fat-induced insulin resistance by salicylate., J Clin Invest, 108, 437, 10.1172/JCI11559
Berg, 2001, The adipocyte-secreted protein Acrp30 enhances hepatic insulin action., Nat Med, 7, 947, 10.1038/90992
Yamauchi, 2001, The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity., Nat Med, 7, 941, 10.1038/90984
Ouchi, 2000, Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-κB signaling through a cAMP-dependent pathway., Circulation, 102, 1296, 10.1161/01.CIR.102.11.1296
Hundal, 2001, Potential for a novel class of insulin sensitizing agents by inhibition of IKKβ activity, Diabetes, 50, A117
Burks, 2001
Aspinwall, 2000, Roles of insulin receptor substrate-1, phosphatidylinositol 3-kinase, and release of intracellular Ca2+ stores in insulin-stimulated insulin secretion in β-cells., J Biol Chem, 275, 22331, 10.1074/jbc.M909647199
Porzio, 1999, The Gly972→Arg amino acid polymorphism in IRS-1 impairs insulin secretion in pancreatic β cells., J Clin Invest, 104, 357, 10.1172/JCI5870
Kulkarni, 1999, Tissue-specific knockout of the insulin receptor in pancreatic β cells creates an insulin secretory defect similar to that in type 2 diabetes., Cell, 96, 329, 10.1016/S0092-8674(00)80546-2
Heffetz, 1990, The insulinomimetic agents H2O2 and vanadate stimulate protein tyrosine phosphorylation in intact cells., J Biol Chem, 265, 2896, 10.1016/S0021-9258(19)39885-0
Denu, 1998, Specific and reversible inactivation of protein tyrosine phosphatases by hydrogen peroxide: evidence for a sulfenic acid intermediate and implications for redox regulation., Biochemistry, 37, 5633, 10.1021/bi973035t
Krejsa, 1998, Impact of oxidative stress on signal transduction control by phosphotyrosine phosphatases., Environ Health Perspect, 106, 1179
Tonks, 2001, Combinatorial control of the specificity of protein tyrosine phosphatases., Curr Opin Cell Biol, 13, 182, 10.1016/S0955-0674(00)00196-4
Hunter, 1998, The Croonian Lecture 1997. The phosphorylation of proteins on tyrosine: its role in cell growth and disease., Philos Trans R Soc Lond B Biol Sci, 353, 583, 10.1098/rstb.1998.0228
Goldstein, 1998, Regulation of the insulin signalling pathway by cellular protein-tyrosine phosphatases., Mol Cell Biochem, 182, 91, 10.1023/A:1006812218502
Keyse, 2000, Protein phosphatases and the regulation of mitogen-activated protein kinase signalling., Curr Opin Cell Biol, 12, 186, 10.1016/S0955-0674(99)00075-7
Pestell, 2000, Small molecule inhibitors of dual specificity protein phosphatases., Oncogene, 19, 6607, 10.1038/sj.onc.1204084
Keyse, 1999, The role of protein phosphatases in the regulation of mitogen and stress-activated protein kinases., Free Radic Res, 31, 341, 10.1080/10715769900300911
Frost, 1985, Evidence for the involvement of vicinal sulfhydryl groups in insulin-activated hexose transport by 3T3–L1 adipocytes., J Biol Chem, 260, 2646, 10.1016/S0021-9258(18)89409-1
Henriksen, 1990, Effects of phenylarsine oxide on stimulation of glucose transport in rat skeletal muscle, Am J Physiol, 258, C648, 10.1152/ajpcell.1990.258.4.C648
Mahadev, 2001, Insulin-stimulated hydrogen peroxide reversibly inhibits protein-tyrosine phosphatase 1B in vivo and enhances the early insulin action cascade., J Biol Chem, 276, 21938, 10.1074/jbc.C100109200
Wrobel, 1998, Novel 5-(3-aryl-2-propynyl)-5-(arylsulfonyl)thiazolidine-2,4-diones as antihyperglycemic agents., J Med Chem, 41, 1084, 10.1021/jm9706168
Malamas, 2001, Antihyperglycemic activity of new 1,2,4-oxadiazolidine-3,5-diones., Eur J Med Chem, 36, 31, 10.1016/S0223-5234(00)01191-0
Malamas, 2000, Novel benzofuran and benzothiophene biphenyls as inhibitors of protein tyrosine phosphatase 1B with antihyperglycemic properties., J Med Chem, 43, 1293, 10.1021/jm990560c
Evans, 1999, Protein tyrosine phosphatases: their role in insulin action and potential as drug targets., Expert Opin Investig Drugs, 8, 139, 10.1517/13543784.8.2.139
Goldstein, 2001, Protein-tyrosine phosphatase 1B (PTP1B): a novel therapeutic target for type 2 diabetes mellitus, obesity, and related states of insulin resistance., Curr Drug Targets, 1, 265
Sims, 1973, Endocrine and metabolic effects of experimental obesity in man., Recent Prog Horm Res, 29, 457
Ferrannini, 1997, Insulin resistance and hypersecretion in obesity. European Group for the Study of Insulin Resistance (EGIR)., J Clin Invest, 100, 1166, 10.1172/JCI119628
Hotamisligil, 1994, Tumor necrosis factor α: a key component of the obesity-diabetes link., Diabetes, 43, 1271, 10.2337/diab.43.11.1271
Moller, 2000, Potential role of TNF-α in the pathogenesis of insulin resistance and type 2 diabetes., Trends Endocrinol Metab, 11, 212, 10.1016/S1043-2760(00)00272-1
Hube, 1999, The role of TNF-α in human adipose tissue: prevention of weight gain at the expense of insulin resistance?, Horm Metab Res, 31, 626, 10.1055/s-2007-978810
Cohen, 1996, Modulation of insulin activities by leptin., Science, 274, 1185, 10.1126/science.274.5290.1185
Müller, 1997, Leptin impairs metabolic actions of insulin in isolated rat adipocytes., J Biol Chem, 272, 10585, 10.1074/jbc.272.16.10585
Randle, 1988, Mechanisms decreasing glucose oxidation in diabetes and starvation: role of lipid fuels and hormones., Diabetes Metab Rev, 623, 638
McGarry, 1992, What if Minkowski had been ageusic? An alternative angle on diabetes., Science, 258, 766, 10.1126/science.1439783
Boden, 1997, Role of fatty acids in the pathogenesis of insulin resistance and NIDDM., Diabetes, 46, 3, 10.2337/diab.46.1.3
Saloranta, 1996, Interactions between glucose and FFA metabolism in man., Diabetes Metab Rev, 12, 15, 10.1002/(SICI)1099-0895(199603)12:1<15::AID-DMR155>3.0.CO;2-0
Foley, 1992, Rationale and application of fatty acid oxidation inhibitors in treatment of diabetes mellitus., Diabetes Care, 15, 773, 10.2337/diacare.15.6.773
Bergman, 2000, Free fatty acids and pathogenesis of type 2 diabetes mellitus., Trends Endocrinol Metab, 11, 351, 10.1016/S1043-2760(00)00323-4
Shulman, 2000, Cellular mechanisms of insulin resistance., J Clin Invest, 106, 171, 10.1172/JCI10583
McGarry, 1999, Fatty acids, lipotoxicity and insulin secretion., Diabetologia, 42, 128, 10.1007/s001250051130
Santomauro, 1999, Overnight lowering of free fatty acids with Acipimox improves insulin resistance and glucose tolerance in obese diabetic and nondiabetic subjects., Diabetes, 48, 1836, 10.2337/diabetes.48.9.1836
Gordon, 1960, Non-esterified fatty acids in blood of obese and lean subjects., J Clin Nutr, 8, 740, 10.1093/ajcn/8.5.740
Reaven, 1988, Measurement of plasma glucose, free fatty acid, lactate, and insulin for 24 h in patients with NIDDM., Diabetes, 37, 1020, 10.2337/diab.37.8.1020
Frayn, 1993, Insulin resistance and lipid metabolism., Curr Opin Lipidol, 4, 197, 10.1097/00041433-199306000-00004
Perseghin, 1997, Metabolic defects in lean nondiabetic offspring of NIDDM parents: a cross-sectional study., Diabetes, 46, 1001, 10.2337/diab.46.6.1001
Pan, 1997, Skeletal muscle triglyceride levels are inversely related to insulin action., Diabetes, 46, 983, 10.2337/diab.46.6.983
Krssak, 1999, Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a H-1 NMR spectroscopy study., Diabetologia, 42, 113, 10.1007/s001250051123
Perseghin, 1999, Intramyocellular triglyceride content is a determinant of in vivo insulin resistance in humans: a 1H–13C nuclear magnetic resonance spectroscopy assessment in offspring of type 2 diabetic parents., Diabetes, 48, 1600, 10.2337/diabetes.48.8.1600
Jacob, 1999, Association of increased intramyocellular lipid content with insulin resistance in lean nondiabetic offspring of type 2 diabetic subjects., Diabetes, 48, 1113, 10.2337/diabetes.48.5.1113
Phillips, 1996, Intramuscular triglyceride and muscle insulin sensitivity: evidence for a relationship in nondiabetic subjects., Metabolism, 45, 947, 10.1016/S0026-0495(96)90260-7
Szczepaniak, 1999, Measurement of intracellular triglyceride stores by H spectroscopy: validation in vivo, Am J Physiol, 276, E977
Boden, 2001, Effects of acute changes of plasma free fatty acids on intramyocellular fat content and insulin resistance in healthy subjects., Diabetes, 50, 1612, 10.2337/diabetes.50.7.1612
Forouhi, 1999, Relation of triglyceride stores in skeletal muscle cells to central obesity and insulin sensitivity in European and South Asian men., Diabetologia, 42, 932, 10.1007/s001250051250
McGarry, 2002, Banting lecture 2001: dysregulation of fatty acid metabolism in the etiology of type 2 diabetes., Diabetes, 51, 7, 10.2337/diabetes.51.1.7
Ruderman, 1999, Malonyl-CoA, fuel sensing, and insulin resistance, Am J Physiol Endocrinol Metab, 39, E1, 10.1152/ajpendo.1999.276.1.E1
Unger, 2000, 132
Bakker, 2000, Cytosolic triglycerides and oxidative stress in central obesity: the missing link between excessive atherosclerosis, endothelial dysfunction, and β-cell failure?, Atherosclerosis, 148, 17, 10.1016/S0021-9150(99)00329-9
Randle, 1966, Carbohydrate metabolism and lipid storage and breakdown in diabetes., Diabetologia, 2, 237, 10.1007/BF01268180
Randle, 1994, Mechanisms modifying glucose oxidation in diabetes mellitus, Diabetologia, 37, S155, 10.1007/BF00400839
Roden, 1996, Mechanism of free fatty acid-induced insulin resistance in humans., J Clin Invest, 97, 2859, 10.1172/JCI118742
Dresner, 1999, Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylinositol 3-kinase activity., J Clin Invest, 103, 253, 10.1172/JCI5001
Schmitz-Peiffer, 2000, Signalling aspects of insulin resistance in skeletal muscle: mechanisms induced by lipid oversupply., Cell Signal, 12, 583, 10.1016/S0898-6568(00)00110-8
Osada, 1992, A new member of the protein kinase C family, nPKCθ, predominantly expressed in skeletal muscle., Mol Cell Biol, 12, 3930, 10.1128/MCB.12.9.3930
Chang, 1993, Molecular cloning and expression of a cDNA encoding a novel isoenzyme of protein kinase C (nPKC). A new member of the nPKC family expressed in skeletal muscle, megakaryoblastic cells, and platelets., J Biol Chem, 268, 14208, 10.1016/S0021-9258(19)85228-6
Toborek, 1994, Fatty acid-mediated effects on the glutathione redox cycle in cultured endothelial cells., Am J Clin Nutr, 59, 60, 10.1093/ajcn/59.1.60
Hennig, 2000, Fatty acid-mediated activation of vascular endothelial cells., Metabolism, 49, 1006, 10.1053/meta.2000.7736
Toborek, 2002, Unsaturated fatty acids selectively induce an inflammatory environment in human endothelial cells., Am J Clin Nutr, 75, 119, 10.1093/ajcn/75.1.119
Dichtl, 1999, Very low-density lipoprotein activates nuclear factor-κB in endothelial cells., Circ Res, 84, 1085, 10.1161/01.RES.84.9.1085
Toborek, 1999, Arachidonic acid-induced oxidative injury to cultured spinal cord neurons., J Neurochem, 73, 684, 10.1046/j.1471-4159.1999.0730684.x
Hennig, 1999, Antioxidant-like properties of zinc in activated endothelial cells., J Am Coll Nutr, 18, 152, 10.1080/07315724.1999.10718843
Blondeau, 2001, Activation of the nuclear factor-κB is a key event in brain tolerance., J Neurosci, 21, 4668, 10.1523/JNEUROSCI.21-13-04668.2001
Lee, 2001, Saturated fatty acids, but not unsaturated fatty acids, induce the expression of cyclooxygenase-2 mediated through Toll-like receptor 4., J Biol Chem, 276, 16683, 10.1074/jbc.M011695200
Coudronniere, 2000, NF-κB activation induced by T cell receptor/CD28 costimulation is mediated by protein kinase C-θ., Proc Natl Acad Sci USA, 97, 3394
Hennig, 2001, High-energy diets, fatty acids and endothelial cell function: implications for atherosclerosis., J Am Coll Nutr, 20, 97, 10.1080/07315724.2001.10719021
Duplus, 2000, Fatty acid regulation of gene transcription., J Biol Chem, 275, 30749, 10.1074/jbc.R000015200
Slatter, 2000, The importance of lipid-derived malondialdehyde in diabetes mellitus., Diabetologia, 43, 550, 10.1007/s001250051342
Paolisso, 1996, Does free fatty acid infusion impair insulin action also through an increase in oxidative stress?, J Clin Endocrinol Metab, 81, 4244, 10.1210/jcem.81.12.8954022
Guillam, 2000, Glucose uptake, utilization, and signaling in GLUT2-null islets., Diabetes, 49, 1485, 10.2337/diabetes.49.9.1485
Arbuckle, 1996, Structure-function analysis of liver-type (GLUT2) and brain-type (GLUT3) glucose transporters: Expression of chimeric transporters in Xenopus oocytes suggests an important role for putative transmembrane helix 7 in determining substrate selectivity., Biochemistry, 35, 16519, 10.1021/bi962210n
Pessin, 1992, Mammalian facilitative glucose transporter family: structure and molecular regulation., Annu Rev Physiol, 54, 911, 10.1146/annurev.ph.54.030192.004403
Seatter, 1999, The mammalian facilitative glucose transporter (GLUT) family., Pharm Biotechnol, 12, 201, 10.1007/0-306-46812-3_7
Bedoya, 1986, The glucokinase glucose sensor in human pancreatic islet tissue., Diabetes, 35, 61, 10.2337/diab.35.1.61
Matschinsky, 1990, Glucokinase as glucose sensor and metabolic signal generator in pancreatic β-cells and hepatocytes., Diabetes, 39, 647, 10.2337/diab.39.6.647
Matschinsky, 1996, Banting Lecture 1995. A lesson in metabolic regulation inspired by the glucokinase glucose sensor paradigm., Diabetes, 45, 223, 10.2337/diab.45.2.223
Matschinsky, 1998, Pancreatic β-cell glucokinase: closing the gap between theoretical concepts and experimental realities., Diabetes, 47, 307, 10.2337/diabetes.47.3.307
Meglasson, 1986, Pancreatic islet glucose metabolism and regulation of insulin secretion., Diabetes Metab Rev, 2, 163, 10.1002/dmr.5610020301
Malaisse, 1997, Physiology, pathology and pharmacology of insulin secretion: recent acquisitions, Diabetes Metab, 23, 6
Maechler, 1997, Mitochondrial activation directly triggers the exocytosis of insulin in permeabilized pancreatic β-cells., EMBO J, 16, 3833, 10.1093/emboj/16.13.3833
Wollheim, 2000, β-Cell mitochondria in the regulation of insulin secretion: a new culprit in type II diabetes., Diabetologia, 43, 265, 10.1007/s001250050044
Sakuraba, 2002, Reduced β-cell mass and expression of oxidative stress-related DNA damage in the islet of Japanese type II diabetic patients., Diabetologia, 45, 85, 10.1007/s125-002-8248-z
Maechler, 1999, Hydrogen peroxide alters mitochondrial activation and insulin secretion in pancreatic β cells., J Biol Chem, 274, 27905, 10.1074/jbc.274.39.27905
Laybutt, 2002, Increased expression of antioxidant and antiapoptotic genes in islets that may contribute to β-cell survival during chronic hyperglycemia., Diabetes, 51, 413, 10.2337/diabetes.51.2.413
Weir, 2001, β-Cell adaptation and decompensation during the progression of diabetes, Diabetes, 50, S154, 10.2337/diabetes.50.2007.S154
Kajimoto, 1999, Induction of glycation suppresses glucokinase gene expression in HIT-T15 cells., Diabetologia, 42, 1417, 10.1007/s001250051313
Cardozo, 2001, A comprehensive analysis of cytokine-induced and nuclear factor-κB-dependent genes in primary rat pancreatic β-cells., J Biol Chem, 276, 48879, 10.1074/jbc.M108658200
Robertson, 2000, 125
Poitout, 2002, Minireview: secondary β-cell failure in type 2 diabetes—a convergence of glucotoxicity and lipotoxicity., Endocrinology, 143, 339, 10.1210/endo.143.2.8623
Boden, 1996, Effects of prolonged glucose infusion on insulin secretion, clearance, and action in normal subjects, Am J Physiol, 270, E251
Miyazaki, 2002, Dose-response effect of pioglitazone on insulin sensitivity and insulin secretion in type 2 diabetes., Diabetes Care, 25, 517, 10.2337/diacare.25.3.517
Leibowitz, 2001, β-Cell glucotoxicity in the Psammomys obesus model of type 2 diabetes, Diabetes, 50, S113, 10.2337/diabetes.50.2007.S113
Leahy, 2000, 115
Donath, 1999, Hyperglycemia-induced β-cell apoptosis in pancreatic islets of Psammomys obesus during development of diabetes., Diabetes, 48, 738, 10.2337/diabetes.48.4.738
Robertson, 1992, Preservation of insulin mRNA levels and insulin secretion in HIT cells by avoidance of chronic exposure to high glucose concentrations., J Clin Invest, 90, 320, 10.1172/JCI115865
Poitout, 1996, Chronic exposure of β TC-6 cells to supraphysiologic concentrations of glucose decreases binding of the RIPE3b1 insulin gene transcription activator., J Clin Invest, 97, 1041, 10.1172/JCI118496
Tanaka, 1999, Prevention of glucose toxicity in HIT-T15 cells and Zucker diabetic fatty rats by antioxidants., Proc Natl Acad Sci USA, 96, 10857, 10.1073/pnas.96.19.10857
Liang, 1991, Glucose at physiological levels induces glucokinase, glucose usage, and insulin secretion in cultures pancreatic islets, Diabetes, 40, 177A
Robertson, 1994, Differentiating glucose toxicity from glucose desensitization: a new message from the insulin gene., Diabetes, 43, 1085, 10.2337/diab.43.9.1085
Bolaffi, 1988, Characteristics of desensitization of insulin secretion in fully in vitro systems., Endocrinology, 122, 1801, 10.1210/endo-122-5-1801
Kilpatrick, 1998, Differentiation between glucose-induced desensitization of insulin secretion and β-cell exhaustion in the HIT-T15 cell line., Diabetes, 47, 606, 10.2337/diabetes.47.4.606
Maechler, 1998, Desensitization of mitochondrial Ca2+ and insulin secretion responses in the β cell., J Biol Chem, 273, 20770, 10.1074/jbc.273.33.20770
Cerasi, 1974, A mathematical model for the glucose induced insulin release in man., Eur J Clin Invest, 4, 267, 10.1111/j.1365-2362.1974.tb02345.x
Grodsky, 1968, Factors influencing different rates of insulin release, Acta Diabetol Lat, 1, 140
Liu, 1998, Shared biochemical properties of glucotoxicity and lipotoxicity in islets decrease citrate synthase activity and increase phosphofructokinase activity., Diabetes, 47, 1889, 10.2337/diabetes.47.12.1889
Zhou, 1996, Inhibitory effects of fatty acids on glucose-regulated β-cell function: association with increased islet triglyceride stores and altered effect of fatty acid oxidation on glucose metabolism., Metabolism, 45, 981, 10.1016/S0026-0495(96)90267-X
Zhou, 1995, Long term exposure to fatty acids and ketones inhibits β-cell functions in human pancreatic islets of Langerhans., J Clin Endocrinol Metab, 80, 1584
Briaud, 1999, Long-term exposure of isolated rat islets of Langerhans to supraphysiologic glucose concentrations decreases insulin mRNA levels., Metabolism, 48, 319, 10.1016/S0026-0495(99)90079-3
Maedler, 2001, Distinct effects of saturated and monounsaturated fatty acids on β-cell turnover and function., Diabetes, 50, 69, 10.2337/diabetes.50.1.69
Zhou, 1994, Long-term exposure of rat pancreatic islets to fatty acids inhibits glucose-induced insulin secretion and biosynthesis through a glucose fatty acid cycle., J Clin Invest, 93, 870, 10.1172/JCI117042
Bollheimer, 1998, Chronic exposure to free fatty acid reduces pancreatic β cell insulin content by increasing basal insulin secretion that is not compensated for by a corresponding increase in proinsulin biosynthesis translation., J Clin Invest, 101, 1094, 10.1172/JCI420
Hirose, 1996, Defective fatty acid-mediated β-cell compensation in Zucker diabetic fatty rats. Pathogenic implications for obesity-dependent diabetes., J Biol Chem, 271, 5633, 10.1074/jbc.271.10.5633
Yoshikawa, 2001, Effects of free fatty acids on β-cell functions: a possible involvement of peroxisome proliferator-activated receptors α or pancreatic/duodenal homeobox., Metabolism, 50, 613, 10.1053/meta.2001.22565
Gremlich, 1997, Fatty acids decrease IDX-1 expression in rat pancreatic islets and reduce GLUT2, glucokinase, insulin, and somatostatin levels., J Biol Chem, 272, 30261, 10.1074/jbc.272.48.30261
Lameloise, 2001, Uncoupling protein 2: a possible link between fatty acid excess and impaired glucose-induced insulin secretion?, Diabetes, 50, 803, 10.2337/diabetes.50.4.803
Segall, 1999, Lipid rather than glucose metabolism is implicated in altered insulin secretion caused by oleate in INS-1 cells, Am J Physiol, 277, E521
Unger, 2001, Lipotoxicity of β-cells in obesity and in other causes of fatty acid spillover, Diabetes, 50, S118, 10.2337/diabetes.50.2007.S118
Kawai, 2001, Chronic effects of different fatty acids and leptin in INS-1 cells., Diabetes Res Clin Pract, 51, 1, 10.1016/S0168-8227(00)00201-1
Jacqueminet, 2000, Inhibition of insulin gene expression by long-term exposure of pancreatic β cells to palmitate is dependent on the presence of a stimulatory glucose concentration., Metabolism, 49, 532, 10.1016/S0026-0495(00)80021-9
Harmon, 2001, Antecedent hyperglycemia, not hyperlipidemia, is associated with increased islet triacylglycerol content and decreased insulin gene mRNA level in Zucker diabetic fatty rats., Diabetes, 50, 2481, 10.2337/diabetes.50.11.2481
Briaud, 2002, Differential effects of hyperlipidemia on insulin secretion in islets of Langerhans from hyperglycemic versus normoglycemic rats., Diabetes, 51, 662, 10.2337/diabetes.51.3.662
Benhamou, 1998, Adenovirus-mediated catalase gene transfer reduces oxidant stress in human, porcine and rat pancreatic islets., Diabetologia, 41, 1093, 10.1007/s001250051035
Kaneto, 1999, Oxidative stress induces p21 expression in pancreatic islet cells: possible implication in β-cell dysfunction., Diabetologia, 42, 1093, 10.1007/s001250051276
Rabinovitch, 1996, Human pancreatic islet β-cell destruction by cytokines involves oxygen free radicals and aldehyde production., J Clin Endocrinol Metab, 81, 3197
Ho, 1999, Antioxidants, NFκB activation, and diabetogenesis., Proc Soc Exp Biol Med, 222, 205, 10.1046/j.1525-1373.1999.d01-137.x
Janjic, 1999, Free radical modulation of insulin release in INS-1 cells exposed to alloxan., Biochem Pharmacol, 57, 639, 10.1016/S0006-2952(98)00346-3
Tiedge, 1997, Relation between antioxidant enzyme gene expression and antioxidative defense status of insulin-producing cells., Diabetes, 46, 1733, 10.2337/diab.46.11.1733
Hotta, 2000, 265
Tiedge, 1998, Complementary action of antioxidant enzymes in the protection of bioengineered insulin-producing RINm5F cells against the toxicity of reactive oxygen species., Diabetes, 47, 1578, 10.2337/diabetes.47.10.1578
Kubisch, 1997, Targeted overexpression of Cu/Zn superoxide dismutase protects pancreatic β-cells against oxidative stress., Diabetes, 46, 1563, 10.2337/diabetes.46.10.1563
Miwa, 2000, Inhibition of glucose-induced insulin secretion by 4-hydroxy-2-nonenal and other lipid peroxidation products., Endocrinology, 141, 2767, 10.1210/endo.141.8.7614
Kaneto, 1999, Beneficial effects of antioxidants in diabetes: possible protection of pancreatic β-cells against glucose toxicity., Diabetes, 48, 2398, 10.2337/diabetes.48.12.2398
Tajiri, 1997, Long-term effects of aminoguanidine on insulin release and biosynthesis: evidence that the formation of advanced glycosylation end products inhibits β-cell function., Endocrinology, 138, 273, 10.1210/endo.138.1.4851
Ho, 2001, Dietary zinc supplementation inhibits NFκB activation and protects against chemically induced diabetes in CD1 mice., Exp Biol Med, 226, 103, 10.1177/153537020122600207
Ihara, 2000, Antioxidant α-tocopherol ameliorates glycemic control of GK rats, a model of type 2 diabetes., FEBS Lett, 473, 24, 10.1016/S0014-5793(00)01489-7
Kaneto, 2001, Activation of the hexosamine pathway leads to deterioration of pancreatic β-cell function through the induction of oxidative stress., J Biol Chem, 276, 31099, 10.1074/jbc.M104115200
Meglasson, 1986, Identification of glucokinase as an alloxan-sensitive glucose sensor of the pancreatic β-cell., Diabetes, 35, 1163, 10.2337/diab.35.10.1163
Lenzen, 1988, Inhibition of glucokinase by alloxan through interaction with SH groups in the sugar-binding site of the enzyme., Mol Pharmacol, 34, 395
Tiedge, 1997, Modulation of human glucokinase intrinsic activity by SH reagents mirrors post-translational regulation of enzyme activity., Biochim Biophys Acta, 1337, 175, 10.1016/S0167-4838(96)00162-8
Tiedge, 2000, Importance of cysteine residues for the stability and catalytic activity of human pancreatic β cell glucokinase., Arch Biochem Biophys, 375, 251, 10.1006/abbi.1999.1666
Halliwell, 1995, Antioxidant characterization. Methodology and mechanism., Biochem Pharmacol, 49, 1341, 10.1016/0006-2952(95)00088-H
Ames, 1993, Oxidants, antioxidants, and the degenerative diseases of aging., Proc Natl Acad Sci USA, 90, 7915, 10.1073/pnas.90.17.7915
Ichijo, 1999, From receptors to stress-activated MAP kinases., Oncogene, 18, 6087, 10.1038/sj.onc.1203129
Santerre, 1981, Insulin synthesis in a clonal cell line of simian virus 40-transformed hamster pancreatic β cells., Proc Natl Acad Sci USA, 78, 4339, 10.1073/pnas.78.7.4339
Zhang, 1989, Insulin secretion and cAMP metabolism in HIT cells. Reciprocal and serial passage-dependent relationships., Diabetes, 38, 44, 10.2337/diab.38.1.44
Shimabukuro, 1998, Fatty acid-induced β cell apoptosis: a link between obesity and diabetes., Proc Natl Acad Sci USA, 95, 2498, 10.1073/pnas.95.5.2498
Unger, 1999, Regulation of fatty acid homeostasis in cells: novel role of leptin., Proc Nat Acad Sci USA, 96, 2327, 10.1073/pnas.96.5.2327
Kolesnick, 1998, Regulation of ceramide production and apoptosis., Annu Rev Physiol, 60, 643, 10.1146/annurev.physiol.60.1.643
Hannun, 2000, Ceramide in the eukaryotic stress response., Trends Cell Biol, 10, 73, 10.1016/S0962-8924(99)01694-3