Molecular aspects of lipoic acid in the prevention of diabetes complications

alpha -Lipoic acid (LA) and its reduced form, dihydrolipoic acid, are power ful antioxidants, LA scavenges hydroxyl radicals, hypochlorous acid, peroxy nitrite, and singlet oxygen. Dihydrolipoic acid also scavenges superoxide a nd peroxyl radicals and can regenerate thioredoxin, vitamin C, and glutathi one, which in turn can recycle vitamin E. There are several possible source s of oxidative stress in diabetes including glycation reactions, decompartm entalization of transition metals, and a shift in the reduced-oxygen status of the diabetic cells. Diabetics have increased levels of lipid hydroperox ides, DNA adducts, and protein carbonyls. Available data strongly suggest t hat LA, because of its antioxidant properties, is particularly suited to th e prevention and/or treatment of diabetic complications that arise from an overproduction of reactive oxygen and nitrogen species. In addition to its antioxidant properties, LA increases glucose uptake through recruitment of the glucose transporter-4 to plasma membranes, a mechanism that is shared w ith insulin-stimulated glucose uptake. Further, recent trials have demonstr ated that LA improves glucose disposal in patients with type II diabetes. I n experimental and clinical studies, LA markedly reduced the symptoms of di abetic pathologies, including cataract formation, vascular damage, and poly neuropathy. To develop a better understanding of the preventative and thera peutic potentials of LA, much of the current interest is focused on elucida ting its molecular mechanisms in redox dependent gene expression. Nutrition 2001;17:888-895. (C) Elsevier Science Inc. 2001.