Protective effects of R‐alpha‐lipoic acid and acetyl‐L‐carnitine in MIN6 and isolated rat islet cells chronically exposed to oleic acid

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Abstract
Mitochondrial dysfunction due to oxidative stress and concomitant impaired β‐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 β‐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 β‐cell dysfunction and that pretreatment with mitochondrial protective nutrients could be an effective strategy to prevent β‐cell dysfunction. J. Cell. Biochem. 104: 1232–1243, 2008.