2007 JASN IMPACT FACTOR 7.111	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chung, S. S.M. Articles by Chung, S. K. Search for Related Content PubMed PubMed Citation Articles by Chung, S. S.M. Articles by Chung, S. K.

Contribution of Polyol Pathway to Diabetes-Induced Oxidative Stress

Stephen S.M. Chung^*,, Eric C.M. Ho^*, Karen S.L. Lam and Sookja K. Chung^*,

*Institute of Molecular Biology, Institute of Molecular Technology for Drug Discovery and Synthesis, and Department of Medicine, The University of Hong Kong, Hong Long, China.

Correspondence to Dr. Stephen S.M. Chung, 8/F Kadoorie Biological Sciences Building, Institute of Molecular Biology, The University of Hong Kong, Pokfulam, Hong Kong, PR China. Phone: 852-22990782; Fax: 852-28171006;

ABSTRACT. Diabetes causes increased oxidative stress, which is thought to play an important role in the pathogenesis of various diabetic complications. However, the source of the hyperglycemia-induced oxidative stress is not clear. It was found that the polyol pathway is the major contributor to oxidative stress in the lenses and nerves of diabetic mice. The first enzyme in the pathway, aldose reductase (AR), reduces glucose to sorbitol, which is then converted to fructose by sorbitol dehydrogenase (SDH). Transgenic mice that overexpress AR specifically in their lenses showed a significant increase in oxidative stress when they became hyperglycemic, as indicated by a decrease in GSH and an increase in malondialdehyde in their lenses. Introducing an SDH-deficient mutation into these transgenic mice significantly normalized the GSH and malondialdehyde levels. These results indicate that both enzymes of the polyol pathway contributed to hyperglycemia-induced oxidative stress in the lens. In the wild-type mice, diabetes caused a significant decrease in GSH in their sciatic nerves, indicative of oxidative stress. In the AR null mutant mice, diabetes did not lead to any decrease in the nerve GSH level. These results indicate that similar to the situation in the lens, AR is also the major contributor to hyperglycemia-induced oxidative stress in the nerve. Although increased flux of glucose through the polyol pathway leads to diabetic lesions in both the lenses and nerve, the mechanisms may be different. AR-induced osmotic stress seems to be the cause of diabetic cataract, whereas AR-induced oxidative stress is probably the cause of neuronal dysfunction. E-mail: smchung@hkucc.hku.hk

This article has been cited by other articles:

				S. Reungjui, C. A. Roncal, W. Mu, T. R. Srinivas, D. Sirivongs, R. J. Johnson, and T. Nakagawa Thiazide Diuretics Exacerbate Fructose-Induced Metabolic Syndrome J. Am. Soc. Nephrol., October 1, 2007; 18(10): 2724 - 2731. [Abstract] [Full Text] [PDF]

				M. T. Barati, M. L. Merchant, A. B. Kain, A. W. Jevans, K. R. McLeish, and J. B. Klein Proteomic analysis defines altered cellular redox pathways and advanced glycation end-product metabolism in glomeruli of db/db diabetic mice Am J Physiol Renal Physiol, October 1, 2007; 293(4): F1157 - F1165. [Abstract] [Full Text] [PDF]

				Y. Ohshiro, R. C. Ma, Y. Yasuda, J. Hiraoka-Yamamoto, A. C. Clermont, K. Isshiki, K. Yagi, E. Arikawa, T. S. Kern, and G. L. King Reduction of Diabetes-Induced Oxidative Stress, Fibrotic Cytokine Expression, and Renal Dysfunction in Protein Kinase C{beta}-Null Mice Diabetes, November 1, 2006; 55(11): 3112 - 3120. [Abstract] [Full Text] [PDF]

				M. S. Ola, D. A. Berkich, Y. Xu, M. T. King, T. W. Gardner, I. Simpson, and K. F. LaNoue Analysis of glucose metabolism in diabetic rat retinas Am J Physiol Endocrinol Metab, June 1, 2006; 290(6): E1057 - E1067. [Abstract] [Full Text] [PDF]

				J. Asbun and F. J. Villarreal The Pathogenesis of Myocardial Fibrosis in the Setting of Diabetic Cardiomyopathy J. Am. Coll. Cardiol., February 21, 2006; 47(4): 693 - 700. [Abstract] [Full Text] [PDF]

				P. Suryanarayana, M. Saraswat, T. Mrudula, T. P. Krishna, K. Krishnaswamy, and G. B. Reddy Curcumin and Turmeric Delay Streptozotocin-Induced Diabetic Cataract in Rats Invest. Ophthalmol. Vis. Sci., June 1, 2005; 46(6): 2092 - 2099. [Abstract] [Full Text] [PDF]

				M. D. Aleo, C. M. Doshna, and K. A. Navetta Ciglitazone-Induced Lenticular Opacities in Rats: In Vivo and Whole Lens Explant Culture Evaluation J. Pharmacol. Exp. Ther., March 1, 2005; 312(3): 1027 - 1033. [Abstract] [Full Text] [PDF]

				S. A. Phillips, F. A. Sylvester, and J. C. Frisbee Oxidant stress and constrictor reactivity impair cerebral artery dilation in obese Zucker rats Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2005; 288(2): R522 - R530. [Abstract] [Full Text] [PDF]

				Y. C. HWANG, M. KANEKO, S. BAKR, H. LIAO, Y. LU, E. R. LEWIS, S. YAN, S. II, M. ITAKURA, L. RUI, et al. Central role for aldose reductase pathway in myocardial ischemic injury FASEB J, August 1, 2004; 18(11): 1192 - 1199. [Abstract] [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673