Open AccessMitochondria-targeted Antioxidants Protect Pancreatic β-cells against Oxidative Stress and Improve Insulin Secretion in Glucotoxicity and Glucolipotoxicity
Author(s) -
SungJig Lim,
Abdur Rashid,
Miran Jang,
Yeonghwan Kim,
Hyeran Won,
Jeong-Hoon Lee,
Jeong Taek Woo,
Young Seol Kim,
Michael P. Murphy,
Liaquat Ali,
Joohun Ha,
Sung Soo Kim
Publication year - 2011
Publication title -
cellular physiology and biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.486
H-Index - 87
eISSN - 1421-9778
pISSN - 1015-8987
DOI - 10.1159/000335802
Subject(s) - oxidative stress , mitochondrion , intracellular , oxidative phosphorylation , endocrinology , unfolded protein response , medicine , biology , microbiology and biotechnology , chemistry , apoptosis , biochemistry
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.