Abstract
alpha-Lipoic acid (alpha-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 (> or = 500 micromol/l). This study investigated whether alpha-LA has a protective role under oxidative stress in beta-cells and its effect is dose-related. In INS-1 cells treated with alpha-LA (150-1200 micromol/l) for 24 h, alpha-LA itself (> or = 300 micromol/l) induced apoptotic death dose-dependently. However, pre-treatment with 150 and 300 micromol/l alpha-LA reduced the hydrogen peroxide-induced apoptosis in INS-1 cells and isolated islets. alpha-LA alleviated hydrogen peroxide-induced reactive oxygen species production, mitochondrial membrane depolarization and c-JNK activation in beta-cells. alpha-LA induced phosphoinositide 3-kinase-dependent Akt phosphorylation in INS-1 cells. While alpha-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.
Original language | English |
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Pages (from-to) | 68-77 |
Number of pages | 10 |
Journal | Free radical research |
Volume | 43 |
Issue number | 1 |
DOIs | |
Publication status | Published - 2009 Jan |
Bibliographical note
Funding Information:This work was supported by a research grant from the Innovative Research Institute for Cell Therapy, Republic of Korea (A062260) to S.I. and the Korea Research Foundation Grant (KRF-2008-331-E00038) from Korean Government (MOEHRD) to B.L.
All Science Journal Classification (ASJC) codes
- Biochemistry