Molecular aspects of lipoic acid in the prevention of diabetes complications.
Alpha-lipoic acid (LA) and its reduced form, dihydrolipoic acid, are powerful antioxidants. LA scavenges hydroxyl radicals, hypochlorous acid, peroxynitrite, and singlet oxygen. Dihydrolipoic acid also scavenges superoxide and peroxyl radicals and can regenerate thioredoxin, vitamin C, and glutathione, which in turn can recycle vitamin E. There are several possible sources of oxidative stress in diabetes including glycation reactions, decompartmentalization of transition metals, and a shift in the reduced-oxygen status of the diabetic cells. Diabetics have increased levels of lipid hydroperoxides, DNA adducts, and protein carbonyls. Available data strongly suggest that LA, because of its antioxidant properties, is particularly suited to the 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 with insulin-stimulated glucose uptake. Further, recent trials have demonstrated that LA improves glucose disposal in patients with type II diabetes. In experimental and clinical studies, LA markedly reduced the symptoms of diabetic pathologies, including cataract formation, vascular damage, and polyneuropathy. To develop a better understanding of the preventative and therapeutic potentials of LA, much of the current interest is focused on elucidating its molecular mechanisms in redox dependent gene expression.
Packer
L
L
Department of Molecular Pharmacology and Toxicology, School of Pharmacy, University of Southern California, 1985 Zonal Avenue, Los Angeles, CA 90098-9121, USA. packerresearch@aol.com
Kraemer
K
K
Rimbach
G
G
D000975:Antioxidants / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001682:Biological Availability; D002386:Cataract / Q000209:etiology / Q000517:prevention & control; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000517:prevention & control*; D003925:Diabetic Angiopathies / Q000209:etiology / Q000517:prevention & control; D003929:Diabetic Neuropathies / Q000209:etiology / Q000517:prevention & control; D005609:Free Radicals / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D008063:Thioctic Acid / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000975:Antioxidants; D005609:Free Radicals; D017382:Reactive Oxygen Species; D008063:Thioctic Acid; D005947:Glucose