Abstract
Mitochondrial oxidative damage is thought to play a key role in pancreatic β-cell failure in the pathogenesis of type 2 diabetes. Despite this, the potential of mitochondria-targeted antioxidants to protect pancreatic β-cells against oxidative stress has not yet been studied. Therefore, we investigated if mitochondria-targeted antioxidants protect pancreatic β-cells such as RINm5F and HIT-T15 cells against oxidative stress under glucotoxic and glucolipotoxic conditions. When β-cells were incubated under these conditions, the expression levels of mitochondrial electron transport chain complex subunits, mitochondrial antioxidant enzymes (such as MnSOD and Prx3), β-cell apoptosis, lipogenic enzymes (such as ACC, FAS and ABCA1), intracellular lipid accumulation, oxidative stress, ER stress, mitochondrial membrane depolarization, nuclear NF- κB 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 β-cells against oxidative stress, promote their survival, and increase insulin secretion in cell models of the glucotoxicity and glucolipotoxicity associated with Type 2 diabetes.
Original language | English (US) |
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Pages (from-to) | 873-886 |
Number of pages | 14 |
Journal | Cellular Physiology and Biochemistry |
Volume | 28 |
Issue number | 5 |
DOIs | |
State | Published - 2011 |
Externally published | Yes |
Bibliographical note
Funding Information:This work was funded by 973 Program of China under Grants No. 2014CB340401 and 2012CB316303, 863 Program of China under Grants No. 2014AA015204, the National Natural Science Foundation of China (NSFC) under Grants No. 61232010, 61472401, 61433014, 61425016, 61203298, and 61572473, Key Research Program of the Chinese Academy of Sciences under Grant No. KGZD-EW-T03-2, and Youth Innovation Promotion Association CAS under Grants No. 20144310 and 2016102.
Keywords
- ER stress
- Lipid peroxidation
- Lipogenesis
- Mitochondrial electron transport chain
- Mitochondrial reactive oxygen species
- Pancreatic β-cell failure
- Type 2 diabetes