title: Mitochondria-targeted antioxidants protect pancreatic β-cells against oxidative stress and improve insulin secretion in glucotoxicity and glucolipotoxicity.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical Science and Engineering Research Center for Bioreaction to Reactive Oxygen Species and Biomedical Science Institute (BK-21), School of Medicine, Kyung Hee University, Seoul, Korea.
authors.forename: Sangbin
authors.initials: S
authors.lastname: Lim
authors.forename: Md Abdur
authors.initials: MA
authors.lastname: Rashid
authors.forename: Miran
authors.initials: M
authors.lastname: Jang
authors.forename: Yeonghwan
authors.initials: Y
authors.lastname: Kim
authors.forename: Hyeran
authors.initials: H
authors.lastname: Won
authors.forename: Jeonghoon
authors.initials: J
authors.lastname: Lee
authors.forename: Jeong-taek
authors.initials: JT
authors.lastname: Woo
authors.forename: Young Seol
authors.initials: YS
authors.lastname: Kim
authors.forename: Michael P
authors.initials: MP
authors.lastname: Murphy
authors.forename: Liaquat
authors.initials: L
authors.lastname: Ali
authors.forename: Joohun
authors.initials: J
authors.lastname: Ha
authors.forename: Sung Soo
authors.initials: SS
authors.lastname: Kim
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002460:Cell Line; D006224:Cricetinae; D005947:Glucose / Q000633:toxicity*; D018398:Homeodomain Proteins / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D051336:Mitochondrial Membranes / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D009943:Organophosphorus Compounds / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014451:Ubiquinone / Q000494:pharmacology / Q000031:analogs & derivatives
chemical_list: D000975:Antioxidants; D018398:Homeodomain Proteins; D007328:Insulin; D016328:NF-kappa B; D009943:Organophosphorus Compounds; C109465:Shox2 protein, rat; D051780:Sterol Regulatory Element Binding Protein 1; D014451:Ubiquinone; C429014:mitoquinone; D013482:Superoxide Dismutase; D005947:Glucose