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

J Cell Biochem. 2008 Jul 1;104(4):1232-43. doi: 10.1002/jcb.21701.


Mitochondrial dysfunction due to oxidative stress and concomitant impaired beta-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 beta-cell dysfunction and that pretreatment with mitochondrial protective nutrients could be an effective strategy to prevent beta-cell dysfunction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcarnitine / pharmacology*
  • Animals
  • Cell Line, Tumor
  • Insulinoma / pathology
  • Islets of Langerhans / drug effects*
  • Islets of Langerhans / pathology
  • Mitochondrial Diseases / drug therapy*
  • Mitochondrial Diseases / pathology
  • Mitochondrial Diseases / prevention & control
  • Oleic Acid / adverse effects*
  • Protective Agents / pharmacology*
  • Rats
  • Thioctic Acid / pharmacology*


  • Protective Agents
  • Oleic Acid
  • Acetylcarnitine
  • Thioctic Acid