Mitochondria-targeted Antioxidants Protect Pancreatic beta-cells against Oxidative Stress and Improve Insulin Secretion in Glucotoxicity and Glucolipotoxicity

作者：Lim Sangbin; Rashid Md Abdur; Jang Miran; Kim Yeonghwan; Won Hyeran; Lee Jeonghoon; Woo Jeong taek; Kim Young Seol; Murphy Michael P; Ali Liaquat; Ha Joohun; Kim Sung Soo^*

来源：Cellular Physiology and Biochemistry, 2011, 28(5): 873-886.

DOI：10.1159/000335802

• Mitochondrial electron transport chain
• Mitochondrial reactive oxygen species
• Lipogenesis
• Lipid peroxidation
• ER stress
• Pancreatic beta-cell failure
• Type 2 diabetes

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.

• 出版日期2011