Mitochondria-targeted antioxidants protect pancreatic β-cells against oxidative stress and improve insulin secretion in glucotoxicity and glucolipotoxicity

Sangbin Lim, Md Abdur Rashid, Miran Jang, Yeonghwan Kim, Hyeran Won, Jeonghoon Lee, Jeong Taek Woo, Young Seol Kim, Michael P. Murphy, Liaquat Ali, Joohun Ha, Sung Soo Kim

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

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 languageEnglish (US)
Pages (from-to)873-886
Number of pages14
JournalCellular Physiology and Biochemistry
Volume28
Issue number5
DOIs
StatePublished - 2011

Keywords

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

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