Dose-related cytoprotective effect of alpha-lipoic acid on hydrogen peroxide-induced oxidative stress to pancreatic beta cells.
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.
Lee
Byung Wan
BW
Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Republic of Korea.
Kwon
Soo Jin
SJ
Chae
Hee Young
HY
Kang
Jun Goo
JG
Kim
Chul Sik
CS
Lee
Seong Jin
SJ
Yoo
Hyung Joon
HJ
Kim
Jae Hyeon
JH
Park
Kyong Soo
KS
Ihm
Sung-Hee
SH
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019610:Cytoprotection / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005947:Glucose / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D008063:Thioctic Acid / Q000494:pharmacology*
D000975:Antioxidants; D007328:Insulin; D008063:Thioctic Acid; D006861:Hydrogen Peroxide; D048031:JNK Mitogen-Activated Protein Kinases; D005947:Glucose