Journal
JOURNAL OF CELLULAR BIOCHEMISTRY
Volume 104, Issue 4, Pages 1232-1243Publisher
WILEY-LISS
DOI: 10.1002/jcb.21701
Keywords
acetyl-L-carnitine; insulin secretion; R-alpha-lipoic acid; mitochondria; oxidative stress; uncoupling protein (UCP)-2; beta-cell
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Mitochondrial dysfunction due to oxidative stress and concomitant impaired P-cell function may play a key role in type 2 diabetes. Preventing and/or ameliorating oxidative mitochondrial dysfunction with mitochondria-specific nutrients may have preventive or therapeutic potential. In the present study, the oxidative mechanism of mitochondrial dysfunction in pancreatic beta-cells exposed to sublethal levels of oleic acid (OA) and the protective effects of mitochondrial nutrients [R-alpha-lipoic acid (LA) and acetyl-L-carnitine (ALC)] were investigated. Chronic exposure (72 h) of insulinoma MIN6 cells to OA (0.2-0.8 mM) increased intracellular oxidant formation, decreased mitochondrial membrane potential (MMP), enhanced uncoupling protein-2 (UCP-2) mRNA and protein expression, and consequently, decreased glucose-induced ATP production and suppressed glucose-stimulated insulin secretion. Pretreatment with LA and/or ALC reduced oxidant formation, increased MMP, regulated UCP-2 mRNA and protein expression, increased glucose-induced ATP production, and restored glucose-stimulated insulin secretion. The key findings on ATP production and insulin secretion were verified with isolated rat islets. These results suggest that mitochondrial dysfunction is involved in OA-induced pancreatic P-cell dysfunction and that Pretreatment with mitochondrial protective nutrients could be an effective strategy to prevent P-cell dysfunction.
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