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Oxidative Stress in the Pathogenesis of Diabetic Neuropathy

Department of Neurology (A.M.V., J.W.R., E.L.F.), University of Michigan, Ann Arbor, Michigan 48109; and Department of Neurology (P.L.), Mayo Clinic, Rochester, Minnesota 55905

Correspondence: Address all correspondence and requests for reprints to: Andrea M. Vincent, Ph.D., Department of Neurology, University of Michigan, Room 4414, Kresge III, 200 Zina Pitcher Place, Ann Arbor, Michigan 48109. E-mail: andreav{at}umich.edu

Oxidative stress results from a cell or tissue failing to detoxify the free radicals that are produced during metabolic activity. Diabetes is characterized by chronic hyperglycemia that produces dysregulation of cellular metabolism. This review explores the concept that diabetes overloads glucose metabolic pathways, resulting in excess free radical production and oxidative stress. Evidence is presented to support the idea that both chronic and acute hyperglycemia cause oxidative stress in the peripheral nervous system that can promote the development of diabetic neuropathy. Proteins that are damaged by oxidative stress have decreased biological activity leading to loss of energy metabolism, cell signaling, transport, and, ultimately, to cell death. Examination of the data from animal and cell culture models of diabetes, as well as clinical trials of antioxidants, strongly implicates hyperglycemia-induced oxidative stress in diabetic neuropathy. We conclude that striving for superior antioxidative therapies remains essential for the prevention of neuropathy in diabetic patients.

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