Protective effects of R-alpha-lipoic acid and acetyl-L-carnitine in MIN6 and isolated rat islet cells chronically exposed to oleic acid.
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.
Shen
Weili
W
Institute for Nutritional Sciences, Shanghai Institute for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, PR China.
Liu
Kai
K
Tian
Chuan
C
Yang
Lu
L
Li
Xuesen
X
Ren
Jinmin
J
Packer
Lester
L
Head
Elizabeth
E
Sharman
Edward
E
Liu
Jiankang
J
D000108:Acetylcarnitine / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor; D007340:Insulinoma / Q000473:pathology; D007515:Islets of Langerhans / Q000187:drug effects* / Q000473:pathology; D028361:Mitochondrial Diseases / Q000188:drug therapy* / Q000473:pathology / Q000517:prevention & control; D019301:Oleic Acid / Q000009:adverse effects*; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D008063:Thioctic Acid / Q000494:pharmacology*
D020011:Protective Agents; D019301:Oleic Acid; D000108:Acetylcarnitine; D008063:Thioctic Acid