Mitochondria-targeted Antioxidants Protect Pancreatic β-cells against Oxidative Stress and Improve Insulin Secretion in Glucotoxicity and Glucolipotoxicity
Mitochondria-targeted Antioxidants Protect Pancreatic β-cells against Oxidative Stress and Improve Insulin Secretion in Glucotoxicity and Glucolipotoxicity
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DOI：
10.1159/000335802
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发表时间：
2011-01-01
影响因子：
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通讯作者：
Kim, Sung Soo
中科院分区：
文献类型：
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作者：
Lim, Sangbin;Rashid, Md Abdur;Kim, Sung Soo
线粒体氧化损伤被认为在2型糖尿病发病机制中的胰岛β细胞衰竭中起关键作用。尽管如此，针对线粒体的抗氧化剂保护胰岛β细胞免受氧化应激的潜力尚未被研究。因此，我们研究了线粒体靶向抗氧化剂在糖毒和糖毒条件下是否保护胰腺β细胞，如RINm5F和HIT-T15细胞免受氧化应激的影响。在此条件下，β细胞线粒体电子传递链复合体亚单位、线粒体抗氧化酶(如MnSOD和Prx3)、β细胞凋亡、造脂酶(如ACC、Fas和ABCA1)、细胞内脂质堆积、氧化应激、内质网应激、线粒体膜去极化、核核因子-kappaB和固醇调节元件结合蛋白1c(SREBP1c)的表达水平均增加，同时细胞内ATP含量、柠檬酸合成酶活性和葡萄糖刺激的胰岛素分泌减少。这些变化与线粒体氧化应激升高是一致的，与线粒体靶向抗氧化剂MitoTemol或MitoQuone(MitoQ)孵育可阻止这些影响。总而言之，线粒体靶向抗氧化剂保护胰腺β细胞免受氧化应激，促进其存活，并在与2型糖尿病相关的糖毒性和糖脂毒性的细胞模型中增加胰岛素分泌。版权所有(C)2011 S.Karger AG，巴塞尔
Mitochondrial oxidative damage is thought to play a key role in pancreatic beta-cell failure in the pathogenesis of type 2 diabetes. Despite this, the potential of mitochondria-targeted antioxidants to protect pancreatic beta-cells against oxidative stress has not yet been studied. Therefore, we investigated if mitochondria-targeted antioxidants protect pancreatic beta-cells such as RINm5F and HIT-T15 cells against oxidative stress under glucotoxic and glucolipotoxic conditions. When beta-cells were incubated under these conditions, the expression levels of mitochondrial electron transport chain complex subunits, mitochondrial antioxidant enzymes (such as MnSOD and Prx3), beta-cell apoptosis, lipogenic enzymes (such as ACC, FAS and ABCA1), intracellular lipid accumulation, oxidative stress, ER stress, mitochondrial membrane depolarization, nuclear NF-kappa B and sterol regulatory element binding protein 1c (SREBP1c) were all increased, in parallel with decreases in intracellular ATP content, citrate synthase enzymatic activity and glucose-stimulated insulin secretion. These changes were consistent with elevated mitochondrial oxidative stress, and incubation with the mitochondria-targeted antioxidants, MitoTempol or Mitoquinone (MitoQ), prevented these effects. In conclusion, mitochondria-targeted antioxidants protect pancreatic beta-cells against oxidative stress, promote their survival, and increase insulin secretion in cell models of the glucotoxicity and glucolipotoxicity associated with Type 2 diabetes. Copyright (C) 2011 S. Karger AG, Basel