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

Byung Wan Lee, Soo Jin Kwon, Hee Young Chae, Jun Goo Kang, Chul Sik Kim, Seong Jin Lee, Hyung Joon Yoo, Jae Hyeon Kim, Kyong Soo Park, Sung Hee Ihm

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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 languageEnglish
Pages (from-to)68-77
Number of pages10
JournalFree radical research
Volume43
Issue number1
DOIs
Publication statusPublished - 2009 Jan

All Science Journal Classification (ASJC) codes

  • Biochemistry

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    Lee, B. W., Kwon, S. J., Chae, H. Y., Kang, J. G., Kim, C. S., Lee, S. J., Yoo, H. J., Kim, J. H., Park, K. S., & Ihm, S. H. (2009). Dose-related cytoprotective effect of alpha-lipoic acid on hydrogen peroxide-induced oxidative stress to pancreatic beta cells. Free radical research, 43(1), 68-77. https://doi.org/10.1080/10715760802590400