Alpha-lipoic acid: mechanisms of action and beneficial effects in the prevention and treatment of diabetic complications

Abstract

Alpha-lipoic acid (ALA) has been widely prescribed drug for treatment and prevention of diabetic complications since it affects the main pathogenesis links. ALA has many biochemical functions acting as a biological antioxidant, anti-inflammatory properties, metal chelators, reducing the oxidized forms of other antioxidant agents such as vitamin C and E and glutathione, and modulating the signaling transduction of several pathways, like insulin and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB). ALA can protect albumin from glycation, improves the redox state of the plasma and endothelium-dependent vasodilation; induces protein kinase B phosphorylation in vascular endothelial cells; shows a protective effect on oxidative stress-induced apoptosis. In skeletal muscle ALA reduce triglyceride accumulation, enhances expression of the insulin receptor substrate 1 protein and improves insulin sensitivity by activating 5′-AMP-activated protein kinase, recruits glucose transporter type 4 from its storage site in the Golgi to the sarcolemma. Prescription of ALA can have both detrimental and cytoprotective effects on pancreatic β-cells.