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

TitleMitochondria-targeted antioxidants protect pancreatic β-cells against oxidative stress and improve insulin secretion in glucotoxicity and glucolipotoxicity.
Publication TypeJournal Article
Year of Publication2011
AuthorsLim, S, Rashid, MAbdur, Jang, M, Kim, Y, Won, H, Lee, J, Woo, J-taek, Kim, YSeol, Murphy, MP, Ali, L, Ha, J, Kim, SSoo
JournalCell Physiol Biochem
Volume28
Issue5
Pagination873-86
Date Published2011
ISSN1421-9778
KeywordsAnimals, Antioxidants, Cell Line, Cricetinae, Glucose, Homeodomain Proteins, Insulin, Insulin Secretion, Insulin-Secreting Cells, Mitochondria, Mitochondrial Membranes, NF-kappa B, Organophosphorus Compounds, Oxidative Stress, Rats, Sterol Regulatory Element Binding Protein 1, Superoxide Dismutase, Ubiquinone
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.

DOI10.1159/000335802
Alternate JournalCell. Physiol. Biochem.
Citation Key10.1159/000335802
PubMed ID22178940
Grant ListMC_U105663142 / / Medical Research Council / United Kingdom