Lee Byung Wan, Kwon Soo Jin, Chae Hee Young, Kang Jun Goo, Kim Chul Sik, Lee Seong Jin, Yoo Hyung Joon, Kim Jae Hyeon, Park Kyong Soo, Ihm Sung-Hee
Department of Internal Medicine, Hallym University College of Medicine, Chuncheon, Republic of Korea.
Free Radic Res. 2009 Jan;43(1):68-77. doi: 10.1080/10715760802590400.
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.
α-硫辛酸（α-LA）是一种用于治疗糖尿病性多发性神经病变的抗氧化剂，据报道，高浓度（≥500微摩尔/升）时，它会诱导胰腺β细胞中AMP激活的蛋白激酶活化并减少胰岛素分泌。本研究调查了α-LA在β细胞氧化应激状态下是否具有保护作用及其效应是否与剂量相关。在用α-LA（150 - 1200微摩尔/升）处理24小时的INS-1细胞中，α-LA本身（≥300微摩尔/升）会剂量依赖性地诱导凋亡性死亡。然而，用150和300微摩尔/升的α-LA预处理可减少过氧化氢诱导的INS-1细胞和分离胰岛的凋亡。α-LA减轻了过氧化氢诱导的β细胞中活性氧的产生、线粒体膜去极化和c-JNK活化。α-LA在INS-1细胞中诱导了磷酸肌醇3激酶依赖性的Akt磷酸化。虽然α-LA在体外高浓度时对β细胞有害，但在糖尿病等氧化应激状态下，它通过其抗氧化特性以及可能在临床相关浓度下通过Akt磷酸化对β细胞具有潜在的细胞保护作用。
