Oxidative Stress and Stress-Activated Signaling Pathways: A Unifying Hypothesis of Type 2 Diabetes
Joseph L. Evans,
Ira D. Goldfine,
Betty A. Maddux and
Gerold M. Grodsky
University of California at San Francisco (I.D.G., B.A.M. G.M.G.), San Francisco, California 94143; and Medical Research Institute (J.L.E.), San Bruno, California 94066
Correspondence: Address all correspondence and requests for reprints to: Joseph L. Evans, Ph.D., Medical Research Institute, 1001 Bayhill Drive, Suite 208, San Bruno, California 94066. E-mail: jevansphd{at}earthlink.net
In both type 1 and type 2 diabetes, the late diabetic complicationsin nerve, vascular endothelium, and kidney arise from chronicelevations of glucose and possibly other metabolites includingfree fatty acids (FFA). Recent evidence suggests that commonstress-activated signaling pathways such as nuclear factor-B,p38 MAPK, and NH2-terminal Jun kinases/stress-activated proteinkinases underlie the development of these late diabetic complications.In addition, in type 2 diabetes, there is evidence that theactivation of these same stress pathways by glucose and possiblyFFA leads to both insulin resistance and impaired insulin secretion.Thus, we propose a unifying hypothesis whereby hyperglycemiaand FFA-induced activation of the nuclear factor-B, p38 MAPK,and NH2-terminal Jun kinases/stress-activated protein kinasesstress pathways, along with the activation of the advanced glycosylationend-products/receptor for advanced glycosylation end-products,protein kinase C, and sorbitol stress pathways, plays a keyrole in causing late complications in type 1 and type 2 diabetes,along with insulin resistance and impaired insulin secretionin type 2 diabetes. Studies with antioxidants such as vitaminE, -lipoic acid, and N-acetylcysteine suggest that new strategiesmay become available to treat these conditions.
This article has been cited by other articles:
Y. Huo, X. Guo, H. Li, H. Wang, W. Zhang, Y. Wang, H. Zhou, Z. Gao, S. Telang, J. Chesney, et al. Disruption of Inducible 6-Phosphofructo-2-kinase Ameliorates Diet-induced Adiposity but Exacerbates Systemic Insulin Resistance and Adipose Tissue Inflammatory Response
J. Biol. Chem.,
February 5, 2010;
285(6):
3713 - 3721.
[Abstract][Full Text][PDF]
J. Lu, D.-m. Wu, Y.-l. Zheng, B. Hu, Z.-f. Zhang, Q. Ye, C.-m. Liu, Q. Shan, and Y.-j. Wang Ursolic Acid Attenuates D-Galactose-Induced Inflammatory Response in Mouse Prefrontal Cortex through Inhibiting AGEs/RAGE/NF-{kappa}B Pathway Activation
Cereb Cortex,
February 4, 2010;
(2010)
bhq002v1.
[Abstract][Full Text][PDF]
J. F. Ndisang, N. Lane, N. Syed, and A. Jadhav Up-Regulating the Heme Oxygenase System with Hemin Improves Insulin Sensitivity and Glucose Metabolism in Adult Spontaneously Hypertensive Rats
Endocrinology,
February 1, 2010;
151(2):
549 - 560.
[Abstract][Full Text][PDF]
J.-h. Xue, Z. Yuan, Y. Wu, Y. Liu, Y. Zhao, W.-p. Zhang, Y.-l. Tian, W.-m. Liu, Y. Liu, and C. Kishimoto High glucose promotes intracellular lipid accumulation in vascular smooth muscle cells by impairing cholesterol influx and efflux balance
Cardiovasc Res,
January 4, 2010;
(2010)
cvp388v2.
[Abstract][Full Text][PDF]
I. Cetin, C. Berti, and S. Calabrese Role of micronutrients in the periconceptional period
Hum. Reprod. Update,
January 1, 2010;
16(1):
80 - 95.
[Abstract][Full Text][PDF]
M. Nomura, H. Ishii, A. Kawakami, and M. Yoshida Inhibition of hepatic Niemann-Pick C1-like 1 improves hepatic insulin resistance
Am J Physiol Endocrinol Metab,
November 1, 2009;
297(5):
E1030 - E1038.
[Abstract][Full Text][PDF]
S. B. Widenmaier, Z. Ao, S.-J. Kim, G. Warnock, and C. H. S. McIntosh Suppression of p38 MAPK and JNK via Akt-mediated Inhibition of Apoptosis Signal-regulating Kinase 1 Constitutes a Core Component of the {beta}-Cell Pro-survival Effects of Glucose-dependent Insulinotropic Polypeptide
J. Biol. Chem.,
October 30, 2009;
284(44):
30372 - 30382.
[Abstract][Full Text][PDF]
H.-Y. Liu, S. Y. Cao, T. Hong, J. Han, Z. Liu, and W. Cao Insulin Is a Stronger Inducer of Insulin Resistance than Hyperglycemia in Mice with Type 1 Diabetes Mellitus (T1DM)
J. Biol. Chem.,
October 2, 2009;
284(40):
27090 - 27100.
[Abstract][Full Text][PDF]
J. M. Chehade, M. Sheikh-Ali, and A. D. Mooradian The Role of Micronutrients in Managing Diabetes
Diabetes Spectr,
October 1, 2009;
22(4):
214 - 218.
[Abstract][Full Text][PDF]
H.-Y. Liu, T. Hong, G.-B. Wen, J. Han, D. Zuo, Z. Liu, and W. Cao Increased basal level of Akt-dependent insulin signaling may be responsible for the development of insulin resistance
Am J Physiol Endocrinol Metab,
October 1, 2009;
297(4):
E898 - E906.
[Abstract][Full Text][PDF]
F. Song, X. Li, M. Zhang, P. Yao, N. Yang, X. Sun, F. B. Hu, and L. Liu Association Between Heme Oxygenase-1 Gene Promoter Polymorphisms and Type 2 Diabetes in a Chinese Population
Am. J. Epidemiol.,
September 15, 2009;
170(6):
747 - 756.
[Abstract][Full Text][PDF]
M. A. Potenza, F. Addabbo, and M. Montagnani Vascular actions of insulin with implications for endothelial dysfunction
Am J Physiol Endocrinol Metab,
September 1, 2009;
297(3):
E568 - E577.
[Abstract][Full Text][PDF]
N. Li, T. Brun, M. Cnop, D. A. Cunha, D. L. Eizirik, and P. Maechler Transient Oxidative Stress Damages Mitochondrial Machinery Inducing Persistent {beta}-Cell Dysfunction
J. Biol. Chem.,
August 28, 2009;
284(35):
23602 - 23612.
[Abstract][Full Text][PDF]
T. Kondo, I. E. Khattabi, W. Nishimura, D. R. Laybutt, P. Geraldes, S. Shah, G. King, S. Bonner-Weir, G. Weir, and A. Sharma p38 MAPK Is a Major Regulator of MafA Protein Stability under Oxidative Stress
Mol. Endocrinol.,
August 1, 2009;
23(8):
1281 - 1290.
[Abstract][Full Text][PDF]
Q.-L. Ma, F. Yang, E. R. Rosario, O. J. Ubeda, W. Beech, D. J. Gant, P. P. Chen, B. Hudspeth, C. Chen, Y. Zhao, et al. {beta}-Amyloid Oligomers Induce Phosphorylation of Tau and Inactivation of Insulin Receptor Substrate via c-Jun N-Terminal Kinase Signaling: Suppression by Omega-3 Fatty Acids and Curcumin
J. Neurosci.,
July 15, 2009;
29(28):
9078 - 9089.
[Abstract][Full Text][PDF]
M. Bluher, N. Bashan, I. Shai, I. Harman-Boehm, T. Tarnovscki, E. Avinaoch, M. Stumvoll, A. Dietrich, N. Kloting, and A. Rudich Activated Ask1-MKK4-p38MAPK/JNK Stress Signaling Pathway in Human Omental Fat Tissue May Link Macrophage Infiltration to Whole-Body Insulin Sensitivity
J. Clin. Endocrinol. Metab.,
July 1, 2009;
94(7):
2507 - 2515.
[Abstract][Full Text][PDF]
L. Lavie and P. Lavie Molecular mechanisms of cardiovascular disease in OSAHS: the oxidative stress link
Eur. Respir. J.,
June 1, 2009;
33(6):
1467 - 1484.
[Abstract][Full Text][PDF]
H. Fujita, H. Fujishima, S. Chida, K. Takahashi, Z. Qi, Y. Kanetsuna, M. D. Breyer, R. C. Harris, Y. Yamada, and T. Takahashi Reduction of Renal Superoxide Dismutase in Progressive Diabetic Nephropathy
J. Am. Soc. Nephrol.,
June 1, 2009;
20(6):
1303 - 1313.
[Abstract][Full Text][PDF]
S. Nakamura, T. Takamura, N. Matsuzawa-Nagata, H. Takayama, H. Misu, H. Noda, S. Nabemoto, S. Kurita, T. Ota, H. Ando, et al. Palmitate Induces Insulin Resistance in H4IIEC3 Hepatocytes through Reactive Oxygen Species Produced by Mitochondria
J. Biol. Chem.,
May 29, 2009;
284(22):
14809 - 14818.
[Abstract][Full Text][PDF]
H. Liang, B. Balas, P. Tantiwong, J. Dube, B. H. Goodpaster, R. M. O'Doherty, R. A. DeFronzo, A. Richardson, N. Musi, and W. F. Ward Whole body overexpression of PGC-1{alpha} has opposite effects on hepatic and muscle insulin sensitivity
Am J Physiol Endocrinol Metab,
April 1, 2009;
296(4):
E945 - E954.
[Abstract][Full Text][PDF]
H. W. Jeong, K. C. Hsu, J.-W. Lee, M. Ham, J. Y. Huh, H. J. Shin, W. S. Kim, and J. B. Kim Berberine suppresses proinflammatory responses through AMPK activation in macrophages
Am J Physiol Endocrinol Metab,
April 1, 2009;
296(4):
E955 - E964.
[Abstract][Full Text][PDF]
I. Padmalayam, S. Hasham, U. Saxena, and S. Pillarisetti Lipoic Acid Synthase (LASY): A Novel Role in Inflammation, Mitochondrial Function, and Insulin Resistance
Diabetes,
March 1, 2009;
58(3):
600 - 608.
[Abstract][Full Text][PDF]
X. F. Wei, Q. G. Zhou, F. F. Hou, B. Y. Liu, and M. Liang Advanced oxidation protein products induce mesangial cell perturbation through PKC-dependent activation of NADPH oxidase
Am J Physiol Renal Physiol,
February 1, 2009;
296(2):
F427 - F437.
[Abstract][Full Text][PDF]
S. S. Chung, M. Kim, B.-S. Youn, N. S. Lee, J. W. Park, I. K. Lee, Y. S. Lee, J. B. Kim, Y. M. Cho, H. K. Lee, et al. Glutathione Peroxidase 3 Mediates the Antioxidant Effect of Peroxisome Proliferator-Activated Receptor {gamma} in Human Skeletal Muscle Cells
Mol. Cell. Biol.,
January 1, 2009;
29(1):
20 - 30.
[Abstract][Full Text][PDF]
N. Bashan, J. Kovsan, I. Kachko, H. Ovadia, and A. Rudich Positive and Negative Regulation of Insulin Signaling by Reactive Oxygen and Nitrogen Species
Physiol Rev,
January 1, 2009;
89(1):
27 - 71.
[Abstract][Full Text][PDF]
N. Barabutis and A. V. Schally Antioxidant activity of growth hormone-releasing hormone antagonists in LNCaP human prostate cancer line
PNAS,
December 23, 2008;
105(51):
20470 - 20475.
[Abstract][Full Text][PDF]
R. Siekmeier, T. Grammer, and W. Marz Roles of Oxidants, Nitric Oxide, and Asymmetric Dimethylarginine in Endothelial Function
Journal of Cardiovascular Pharmacology and Therapeutics,
December 1, 2008;
13(4):
279 - 297.
[Abstract][PDF]
S. Simone, Y. Gorin, C. Velagapudi, H. E. Abboud, and S. L. Habib Mechanism of Oxidative DNA Damage in Diabetes: Tuberin Inactivation and Downregulation of DNA Repair Enzyme 8-Oxo-7,8-Dihydro-2'-Deoxyguanosine-DNA Glycosylase
Diabetes,
October 1, 2008;
57(10):
2626 - 2636.
[Abstract][Full Text][PDF]
K. J. Chuang, B. A. Coull, A. Zanobetti, H. Suh, J. Schwartz, P. H. Stone, A. Litonjua, F. E. Speizer, and D. R. Gold Particulate Air Pollution as a Risk Factor for ST-Segment Depression in Patients With Coronary Artery Disease
Circulation,
September 23, 2008;
118(13):
1314 - 1320.
[Abstract][Full Text][PDF]
H. A. H. Kataya and A. A. Hamza Red Cabbage (Brassica oleracea) Ameliorates Diabetic Nephropathy in Rats
Evid. Based Complement. Altern. Med.,
September 1, 2008;
5(3):
281 - 287.
[Abstract][Full Text][PDF]
N. Kumashiro, Y. Tamura, T. Uchida, T. Ogihara, Y. Fujitani, T. Hirose, H. Mochizuki, R. Kawamori, and H. Watada Impact of Oxidative Stress and Peroxisome Proliferator-Activated Receptor {gamma} Coactivator-1{alpha} in Hepatic Insulin Resistance
Diabetes,
August 1, 2008;
57(8):
2083 - 2091.
[Abstract][Full Text][PDF]
S. de Ferranti and D. Mozaffarian The Perfect Storm: Obesity, Adipocyte Dysfunction, and Metabolic Consequences
Clin. Chem.,
June 1, 2008;
54(6):
945 - 955.
[Abstract][Full Text][PDF]
R Vinayagamoorthi, Z. Bobby, and M G Sridhar Antioxidants preserve redox balance and inhibit c-Jun-N-terminal kinase pathway while improving insulin signaling in fat-fed rats: evidence for the role of oxidative stress on IRS-1 serine phosphorylation and insulin resistance
J. Endocrinol.,
May 1, 2008;
197(2):
287 - 296.
[Abstract][Full Text][PDF]
V. Poitout and R. P. Robertson Glucolipotoxicity: Fuel Excess and {beta}-Cell Dysfunction
Endocr. Rev.,
May 1, 2008;
29(3):
351 - 366.
[Abstract][Full Text][PDF]
A. V. Gyulkhandanyan, H. Lu, S. C. Lee, A. Bhattacharjee, N. Wijesekara, J. E. M. Fox, P. E. MacDonald, F. Chimienti, F. F. Dai, and M. B. Wheeler Investigation of Transport Mechanisms and Regulation of Intracellular Zn2+ in Pancreatic {alpha}-Cells
J. Biol. Chem.,
April 11, 2008;
283(15):
10184 - 10197.
[Abstract][Full Text][PDF]
M. Corton, J. I. Botella-Carretero, J. A. Lopez, E. Camafeita, J. L. San Millan, H. F. Escobar-Morreale, and B. Peral Proteomic analysis of human omental adipose tissue in the polycystic ovary syndrome using two-dimensional difference gel electrophoresis and mass spectrometry
Hum. Reprod.,
March 1, 2008;
23(3):
651 - 661.
[Abstract][Full Text][PDF]
M. Fernandez, C. Triplitt, E. Wajcberg, A. A. Sriwijilkamol, N. Musi, K. Cusi, R. DeFronzo, and E. Cersosimo Addition of Pioglitazone and Ramipril to Intensive Insulin Therapy in Type 2 Diabetic Patients Improves Vascular Dysfunction by Different Mechanisms
Diabetes Care,
January 1, 2008;
31(1):
121 - 127.
[Abstract][Full Text][PDF]
H. Al-Kateb, A. P. Boright, L. Mirea, X. Xie, R. Sutradhar, A. Mowjoodi, B. Bharaj, M. Liu, J. M. Bucksa, V. L. Arends, et al. Multiple Superoxide Dismutase 1/Splicing Factor Serine Alanine 15 Variants Are Associated With the Development and Progression of Diabetic Nephropathy: The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Genetics Study
Diabetes,
January 1, 2008;
57(1):
218 - 228.
[Abstract][Full Text][PDF]
K. Murao, X. Yu, H. Imachi, W. M. Cao, K. Chen, K. Matsumoto, T. Nishiuchi, N. C. W. Wong, and T. Ishida Hyperglycemia suppresses hepatic scavenger receptor class B type I expression
Am J Physiol Endocrinol Metab,
January 1, 2008;
294(1):
E78 - E87.
[Abstract][Full Text][PDF]
F. Palm, M. L. Onozato, Z. Luo, and C. S. Wilcox Dimethylarginine dimethylaminohydrolase (DDAH): expression, regulation, and function in the cardiovascular and renal systems
Am J Physiol Heart Circ Physiol,
December 1, 2007;
293(6):
H3227 - H3245.
[Abstract][Full Text][PDF]
K. Tsukuda, M. Mogi, J.-M. Li, J. Iwanami, L.-J. Min, A. Sakata, T. Fujita, M. Iwai, and M. Horiuchi Amelioration of Cognitive Impairment in the Type-2 Diabetic Mouse by the Angiotensin II Type-1 Receptor Blocker Candesartan
Hypertension,
December 1, 2007;
50(6):
1099 - 1105.
[Abstract][Full Text][PDF]
J. B. Meigs, M. G. Larson, C. S. Fox, J. F. Keaney Jr., R. S. Vasan, and E. J. Benjamin Association of Oxidative Stress, Insulin Resistance, and Diabetes Risk Phenotypes: The Framingham Offspring Study
Diabetes Care,
October 1, 2007;
30(10):
2529 - 2535.
[Abstract][Full Text][PDF]
P. Newsholme, E. P. Haber, S. M. Hirabara, E. L. O. Rebelato, J. Procopio, D. Morgan, H. C. Oliveira-Emilio, A. R. Carpinelli, and R. Curi Diabetes associated cell stress and dysfunction: role of mitochondrial and non-mitochondrial ROS production and activity
J. Physiol.,
August 15, 2007;
583(1):
9 - 24.
[Abstract][Full Text][PDF]
Y. Lu, X. He, and S. Zhong Cross-species microarray analysis with the OSCAR system suggests an INSR->Pax6->NQO1 neuro-protective pathway in aging and Alzheimer's disease
Nucleic Acids Res.,
July 13, 2007;
35(suppl_2):
W105 - W114.
[Abstract][Full Text][PDF]
A. R. Subauste and C. F. Burant Role of FoxO1 in FFA-induced oxidative stress in adipocytes
Am J Physiol Endocrinol Metab,
July 1, 2007;
293(1):
E159 - E164.
[Abstract][Full Text][PDF]
M. Qatanani and M. A. Lazar Mechanisms of obesity-associated insulin resistance: many choices on the menu
Genes & Dev.,
June 15, 2007;
21(12):
1443 - 1455.
[Abstract][Full Text][PDF]
J. Palming, K. Sjoholm, M. Jernas, T. C. Lystig, A. Gummesson, S. Romeo, L. Lonn, M. Lonn, B. Carlsson, and L. M. S. Carlsson The Expression of NAD(P)H:Quinone Oxidoreductase 1 Is High in Human Adipose Tissue, Reduced by Weight Loss, and Correlates with Adiposity, Insulin Sensitivity, and Markers of Liver Dysfunction
J. Clin. Endocrinol. Metab.,
June 1, 2007;
92(6):
2346 - 2352.
[Abstract][Full Text][PDF]
N. Bashan, K. Dorfman, T. Tarnovscki, I. Harman-Boehm, I. F. Liberty, M. Bluher, S. Ovadia, T. Maymon-Zilberstein, R. Potashnik, M. Stumvoll, et al. Mitogen-Activated Protein Kinases, Inhibitory-{kappa}B Kinase, and Insulin Signaling in Human Omental Versus Subcutaneous Adipose Tissue in Obesity
Endocrinology,
June 1, 2007;
148(6):
2955 - 2962.
[Abstract][Full Text][PDF]
M. Mogensen, K. Sahlin, M. Fernstrom, D. Glintborg, B. F. Vind, H. Beck-Nielsen, and K. Hojlund Mitochondrial Respiration Is Decreased in Skeletal Muscle of Patients With Type 2 Diabetes
Diabetes,
June 1, 2007;
56(6):
1592 - 1599.
[Abstract][Full Text][PDF]
K. Kitiphongspattana, T. A. Khan, K. Ishii-Schrade, M. W. Roe, L. H. Philipson, and H. R. Gaskins Protective role for nitric oxide during the endoplasmic reticulum stress response in pancreatic beta-cells
Am J Physiol Endocrinol Metab,
June 1, 2007;
292(6):
E1543 - E1554.
[Abstract][Full Text][PDF]
H.-Y. Liu, Q. F. Collins, Y. Xiong, F. Moukdar, E. G. Lupo Jr., Z. Liu, and W. Cao Prolonged Treatment of Primary Hepatocytes with Oleate Induces Insulin Resistance through p38 Mitogen-activated Protein Kinase
J. Biol. Chem.,
May 11, 2007;
282(19):
14205 - 14212.
[Abstract][Full Text][PDF]
E. Meugnier, M. Faraj, S. Rome, G. Beauregard, A. Michaut, V. Pelloux, J.-L. Chiasson, M. Laville, K. Clement, H. Vidal, et al. Acute Hyperglycemia Induces a Global Downregulation of Gene Expression in Adipose Tissue and Skeletal Muscle of Healthy Subjects
Diabetes,
April 1, 2007;
56(4):
992 - 999.
[Abstract][Full Text][PDF]
J. E. Deanfield, J. P. Halcox, and T. J. Rabelink Endothelial Function and Dysfunction: Testing and Clinical Relevance
Circulation,
March 13, 2007;
115(10):
1285 - 1295.
[Full Text][PDF]
C. L. Sherry, J. C. O'Connor, J. M. Kramer, and G. G. Freund Augmented Lipopolysaccharide-Induced TNF-{alpha} Production by Peritoneal Macrophages in Type 2 Diabetic Mice Is Dependent on Elevated Glucose and Requires p38 MAPK
J. Immunol.,
January 15, 2007;
178(2):
663 - 670.
[Abstract][Full Text][PDF]
I. F. Benter, M. H. M. Yousif, C. Cojocel, M. Al-Maghrebi, and D. I. Diz Angiotensin-(1-7) prevents diabetes-induced cardiovascular dysfunction
Am J Physiol Heart Circ Physiol,
January 1, 2007;
292(1):
H666 - H672.
[Abstract][Full Text][PDF]
J. Park, S. S. Choe, A H. Choi, K. H. Kim, M. J. Yoon, T. Suganami, Y. Ogawa, and J. B. Kim Increase in Glucose-6-Phosphate Dehydrogenase in Adipocytes Stimulates Oxidative Stress and Inflammatory Signals
Diabetes,
November 1, 2006;
55(11):
2939 - 2949.
[Abstract][Full Text][PDF]
J. J. Senn Toll-like Receptor-2 Is Essential for the Development of Palmitate-induced Insulin Resistance in Myotubes
J. Biol. Chem.,
September 15, 2006;
281(37):
26865 - 26875.
[Abstract][Full Text][PDF]
V. A. Cameron, T. J. Mocatta, A. P. Pilbrow, C. M. Frampton, R. W. Troughton, A. M. Richards, and C. C. Winterbourn Angiotensin Type-1 Receptor A1166C Gene Polymorphism Correlates With Oxidative Stress Levels in Human Heart Failure
Hypertension,
June 1, 2006;
47(6):
1155 - 1161.
[Abstract][Full Text][PDF]
F. Gonzalez, N. S. Rote, J. Minium, and J. P. Kirwan Increased Activation of Nuclear Factor {kappa}B Triggers Inflammation and Insulin Resistance in Polycystic Ovary Syndrome
J. Clin. Endocrinol. Metab.,
April 1, 2006;
91(4):
1508 - 1512.
[Abstract][Full Text][PDF]
F Gonzalez, N S Rote, J Minium, and J P Kirwan In vitro evidence that hyperglycemia stimulates tumor necrosis factor-{alpha} release in obese women with polycystic ovary syndrome.
J. Endocrinol.,
March 1, 2006;
188(3):
521 - 529.
[Abstract][Full Text][PDF]
A. Sriwijitkamol, C. Christ-Roberts, R. Berria, P. Eagan, T. Pratipanawatr, R. A. DeFronzo, L. J. Mandarino, and N. Musi Reduced Skeletal Muscle Inhibitor of {kappa}B{beta} Content Is Associated With Insulin Resistance in Subjects With Type 2 Diabetes: Reversal by Exercise Training
Diabetes,
March 1, 2006;
55(3):
760 - 767.
[Abstract][Full Text][PDF]
J. W. Stephens, D. R. Gable, S. J. Hurel, G. J. Miller, J. A. Cooper, and S. E. Humphries Increased Plasma Markers of Oxidative Stress Are Associated with Coronary Heart Disease in Males with Diabetes Mellitus and with 10-Year Risk in a Prospective Sample of Males
Clin. Chem.,
March 1, 2006;
52(3):
446 - 452.
[Abstract][Full Text][PDF]
E. J. Anderson and P. D. Neufer Type II skeletal myofibers possess unique properties that potentiate mitochondrial H2O2 generation
Am J Physiol Cell Physiol,
March 1, 2006;
290(3):
C844 - C851.
[Abstract][Full Text][PDF]
E. W. Kraegen, A. K. Saha, E. Preston, D. Wilks, A. J. Hoy, G. J. Cooney, and N. B. Ruderman Increased malonyl-CoA and diacylglycerol content and reduced AMPK activity accompany insulin resistance induced by glucose infusion in muscle and liver of rats
Am J Physiol Endocrinol Metab,
March 1, 2006;
290(3):
E471 - E479.
[Abstract][Full Text][PDF]
F. Gonzalez, N. S. Rote, J. Minium, and J. P. Kirwan Reactive Oxygen Species-Induced Oxidative Stress in the Development of Insulin Resistance and Hyperandrogenism in Polycystic Ovary Syndrome
J. Clin. Endocrinol. Metab.,
January 1, 2006;
91(1):
336 - 340.
[Abstract][Full Text][PDF]
M. Jove, A. Planavila, R. M. Sanchez, M. Merlos, J. C. Laguna, and M. Vazquez-Carrera Palmitate Induces Tumor Necrosis Factor-{alpha} Expression in C2C12 Skeletal Muscle Cells by a Mechanism Involving Protein Kinase C and Nuclear Factor-{kappa}B Activation
Endocrinology,
January 1, 2006;
147(1):
552 - 561.
[Abstract][Full Text][PDF]
M. Aragno, R. Mastrocola, C. Medana, F. Restivo, M. G. Catalano, N. Pons, O. Danni, and G. Boccuzzi Up-Regulation of Advanced Glycated Products Receptors in the Brain of Diabetic Rats Is Prevented by Antioxidant Treatment
Endocrinology,
December 1, 2005;
146(12):
5561 - 5567.
[Abstract][Full Text][PDF]
M. Y. Donath, J. A. Ehses, K. Maedler, D. M. Schumann, H. Ellingsgaard, E. Eppler, and M. Reinecke Mechanisms of {beta}-Cell Death in Type 2 Diabetes
Diabetes,
December 1, 2005;
54(suppl_2):
S108 - S113.
[Abstract][Full Text][PDF]
C. Scheede-Bergdahl, M. Penkowa, J. Hidalgo, D. B. Olsen, P. Schjerling, C. Prats, R. Boushel, and F. Dela Metallothionein-Mediated Antioxidant Defense System and Its Response to Exercise Training Are Impaired in Human Type 2 Diabetes
Diabetes,
November 1, 2005;
54(11):
3089 - 3094.
[Abstract][Full Text][PDF]
R Mastrocola, F Restivo, I Vercellinatto, O Danni, E Brignardello, M Aragno, and G Boccuzzi Oxidative and nitrosative stress in brain mitochondria of diabetic rats
J. Endocrinol.,
October 1, 2005;
187(1):
37 - 44.
[Abstract][Full Text][PDF]
M Alves, D A. Cunha, V C. Calegari, M J A Saad, A C. Boschero, L A. Velloso, and E M. Rocha Nuclear factor-{kappa}B and advanced glycation end-products expression in lacrimal glands of aging rats
J. Endocrinol.,
October 1, 2005;
187(1):
159 - 166.
[Abstract][Full Text][PDF]
A. S. Dias, M. Porawski, M. Alonso, N. Marroni, P. S. Collado, and J. Gonzalez-Gallego Quercetin Decreases Oxidative Stress, NF-{kappa}B Activation, and iNOS Overexpression in Liver of Streptozotocin-Induced Diabetic Rats
J. Nutr.,
October 1, 2005;
135(10):
2299 - 2304.
[Abstract][Full Text][PDF]
M. Suematsu, A. Katsuki, Y. Sumida, E. C Gabazza, S. Murashima, K. Matsumoto, N. Kitagawa, H. Akatsuka, Y. Hori, K. Nakatani, et al. Decreased circulating levels of active ghrelin are associated with increased oxidative stress in obese subjects
Eur. J. Endocrinol.,
September 1, 2005;
153(3):
403 - 407.
[Abstract][Full Text][PDF]
F. Gonzalez, J. Minium, N. S. Rote, and J. P. Kirwan Hyperglycemia Alters Tumor Necrosis Factor-{alpha} Release from Mononuclear Cells in Women with Polycystic Ovary Syndrome
J. Clin. Endocrinol. Metab.,
September 1, 2005;
90(9):
5336 - 5342.
[Abstract][Full Text][PDF]
P. W. Franks, J. Luan, I. Barroso, S. Brage, J. L. G. Sanchez, U. Ekelund, M. S. Rios, A. J. Schafer, S. O'Rahilly, and N. J. Wareham Variation in the eNOS Gene Modifies the Association Between Total Energy Expenditure and Glucose Intolerance
Diabetes,
September 1, 2005;
54(9):
2795 - 2801.
[Abstract][Full Text][PDF]
D. K. Jagadeesha, T. E. Lindley, J. DeLeon, R. V. Sharma, F. Miller, and R. C. Bhalla Tempol therapy attenuates medial smooth muscle cell apoptosis and neointima formation after balloon catheter injury in carotid artery of diabetic rats
Am J Physiol Heart Circ Physiol,
September 1, 2005;
289(3):
H1047 - H1053.
[Abstract][Full Text][PDF]
E. Sobngwi, J.-F. Gautier, J.-P. Kevorkian, J.-M. Villette, J.-P. Riveline, S. Zhang, P. Vexiau, S. M. Leal, C. Vaisse, and F. Mauvais-Jarvis High Prevalence of Glucose-6-Phosphate Dehydrogenase Deficiency without Gene Mutation Suggests a Novel Genetic Mechanism Predisposing to Ketosis-Prone Diabetes
J. Clin. Endocrinol. Metab.,
August 1, 2005;
90(8):
4446 - 4451.
[Abstract][Full Text][PDF]
A. A. Banday, A. Marwaha, L. S. Tallam, and M. F. Lokhandwala Tempol Reduces Oxidative Stress, Improves Insulin Sensitivity, Decreases Renal Dopamine D1 Receptor Hyperphosphorylation, and Restores D1 Receptor-G-Protein Coupling and Function in Obese Zucker Rats
Diabetes,
July 1, 2005;
54(7):
2219 - 2226.
[Abstract][Full Text][PDF]
G. Wolf, S. Chen, and F. N. Ziyadeh From the Periphery of the Glomerular Capillary Wall Toward the Center of Disease: Podocyte Injury Comes of Age in Diabetic Nephropathy
Diabetes,
June 1, 2005;
54(6):
1626 - 1634.
[Abstract][Full Text][PDF]
G. A. Martens, Y. Cai, S. Hinke, G. Stange, M. Van de Casteele, and D. Pipeleers Glucose Suppresses Superoxide Generation in Metabolically Responsive Pancreatic {beta} Cells
J. Biol. Chem.,
May 27, 2005;
280(21):
20389 - 20396.
[Abstract][Full Text][PDF]
Y. H. Suh, Y. Kim, J. H. Bang, K. S. Choi, J. W. Lee, W.-H. Kim, T. J. Oh, S. An, and M. H. Jung Analysis of gene expression profiles in insulin-sensitive tissues from pre-diabetic and diabetic Zucker diabetic fatty rats
J. Mol. Endocrinol.,
April 1, 2005;
34(2):
299 - 315.
[Abstract][Full Text][PDF]
J. M. Schattenberg, Y. Wang, R. Singh, R. M. Rigoli, and M. J. Czaja Hepatocyte CYP2E1 Overexpression and Steatohepatitis Lead to Impaired Hepatic Insulin Signaling
J. Biol. Chem.,
March 18, 2005;
280(11):
9887 - 9894.
[Abstract][Full Text][PDF]
D. Veneri, M. Franchini, and E. Bonora Imatinib and Regression of Type 2 Diabetes
N. Engl. J. Med.,
March 10, 2005;
352(10):
1049 - 1050.
[Full Text][PDF]
B. J. Goldstein, K. Mahadev, and X. Wu Redox Paradox: Insulin Action Is Facilitated by Insulin-Stimulated Reactive Oxygen Species With Multiple Potential Signaling Targets
Diabetes,
February 1, 2005;
54(2):
311 - 321.
[Abstract][Full Text][PDF]
M. C. Blendea, D. Jacobs, C. S. Stump, S. I. McFarlane, C. Ogrin, G. Bahtyiar, S. Stas, P. Kumar, Q. Sha, C. M. Ferrario, et al. Abrogation of oxidative stress improves insulin sensitivity in the Ren-2 rat model of tissue angiotensin II overexpression
Am J Physiol Endocrinol Metab,
February 1, 2005;
288(2):
E353 - E359.
[Abstract][Full Text][PDF]
I. Talior, T. Tennenbaum, T. Kuroki, and H. Eldar-Finkelman PKC-{delta}-dependent activation of oxidative stress in adipocytes of obese and insulin-resistant mice: role for NADPH oxidase
Am J Physiol Endocrinol Metab,
February 1, 2005;
288(2):
E405 - E411.
[Abstract][Full Text][PDF]
J. Asbun, A. M. Manso, and F. J. Villarreal Profibrotic influence of high glucose concentration on cardiac fibroblast functions: effects of losartan and vitamin E
Am J Physiol Heart Circ Physiol,
January 1, 2005;
288(1):
H227 - H234.
[Abstract][Full Text][PDF]
Y. Nakatani, H. Kaneto, D. Kawamori, M. Hatazaki, T. Miyatsuka, T.-a. Matsuoka, Y. Kajimoto, M. Matsuhisa, Y. Yamasaki, and M. Hori Modulation of the JNK Pathway in Liver Affects Insulin Resistance Status
J. Biol. Chem.,
October 29, 2004;
279(44):
45803 - 45809.
[Abstract][Full Text][PDF]
J.-D. Luo, Y.-Y. Wang, W.-L. Fu, J. Wu, and A. F. Chen Gene Therapy of Endothelial Nitric Oxide Synthase and Manganese Superoxide Dismutase Restores Delayed Wound Healing in Type 1 Diabetic Mice
Circulation,
October 19, 2004;
110(16):
2484 - 2493.
[Abstract][Full Text][PDF]
T. P. Fleming, W. Y. Kwong, R. Porter, E. Ursell, I. Fesenko, A. Wilkins, D. J. Miller, A. J. Watkins, and J. J. Eckert The Embryo and Its Future
Biol Reprod,
October 1, 2004;
71(4):
1046 - 1054.
[Abstract][Full Text][PDF]
L. De Young, D. Yu, R. M. Bateman, and G. B. Brock Oxidative Stress and Antioxidant Therapy: Their Impact in Diabetes-Associated Erectile Dysfunction
J Androl,
September 1, 2004;
25(5):
830 - 836.
[Abstract][Full Text][PDF]
J. Kaput, K. G. Klein, E. J. Reyes, W. A. Kibbe, C. A. Cooney, B. Jovanovic, W. J. Visek, and G. L. Wolff Identification of genes contributing to the obese yellow Avy phenotype: caloric restriction, genotype, diet x genotype interactions
Physiol Genomics,
August 11, 2004;
18(3):
316 - 324.
[Abstract][Full Text][PDF]
M. A. Abdelmegeed, S. K. Kim, K. J. Woodcroft, and R. F. Novak Acetoacetate Activation of Extracellular Signal-Regulated Kinase 1/2 and p38 Mitogen-Activated Protein Kinase in Primary Cultured Rat Hepatocytes: Role of Oxidative Stress
J. Pharmacol. Exp. Ther.,
August 1, 2004;
310(2):
728 - 736.
[Abstract][Full Text][PDF]
B, 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-
-lipoic acid, and N-acetylcysteine suggest that new strategies may become available to treat these conditions. 
