Dose-related cytoprotective effect of α-lipoic acid on hydrogen peroxide-induced oxidative stress to pancreatic beta cells

α-Lipoic acid (α-LA), an antioxidant used for diabetic polyneuropathy, was reported to induce AMP-activated protein kinase activation and reductions in insulin secretion in pancreatic beta-cells at high concentrations (≥ 500 µmol/l). This study investigated whether α-LA has a protective role under oxidative stress in beta-cells and its effect is dose-related. In INS-1 cells treated with α-LA (150-1200 µmol/l) for 24 h, α-LA itself (≥300 µmol/l) induced apoptotic death dose-dependently. However, pre-treatment with 150 and 300 µmol/l α-LA reduced the hydrogen peroxide-induced apoptosis in INS-1 cells and isolated islets. α-LA alleviated hydrogen peroxide-induced reactive oxygen species production, mitochondrial membrane depolarization and c-JNK activation in beta-cells. α-LA induced phosphoinositide 3-kinase-dependent Akt phosphorylation in INS-1 cells. While α-LA is harmful to beta-cells at high concentrations in vitro, it has potential cytoprotective effects on beta-cells under oxidative stress as in diabetes by its antioxidant properties and possibly by Akt phosphorylation at clinically relevant concentrations.