Oxidative stress-induced insulin resistance in skeletal muscle cells is ameliorated by gamma-tocopherol treatment.
BACKGROUND
Oxidative stress-induced reactive oxygen species are associated with the clinical manifestation of insulin resistance. Evidence suggests that antioxidant treatment may reduce this incidence.


OBJECTIVE
This study determined whether glucose oxidase (GO)-induced insulin resistance in cultured skeletal muscle cells could be ameliorated by pre-treatment with gamma-tocopherol (GT).


METHODS
Insulin sensitivity in L6 myotubes was assessed by 2-deoxy-D: -[(3)H]-glucose uptake. The phosphorylation of distal insulin signaling proteins Akt and the Akt substrate AS160 were determined by western blot.


RESULTS
One hour treatment with 100 mU/ml GO decreased insulin-stimulated glucose uptake (P < 0.001). Pre-treatment with GT either partially (100 microM) or completely (200 microM) restored insulin-stimulated glucose uptake in cells after GO-induced insulin resistance. GO-induced oxidative stress did not impair insulin stimulated phosphorylation of Akt or AS160, but 200 microM GT increased insulin-stimulated phosphorylation of these key signaling proteins (P < 0.05).


CONCLUSIONS
High-dose (200 microM) GT treatment ameliorated oxidative stress-induced insulin resistance in cultured rat L6 skeletal muscle cells.
Singh
Indu
I
Exercise Metabolism Group, School of Medical Sciences, RMIT University, PO Box 71, Bundoora, VIC, 3083, Australia.
Carey
Andrew L
AL
Watson
Nadine
N
Febbraio
Mark A
MA
Hawley
John A
JA
D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D015153:Blotting, Western; D002478:Cells, Cultured; D005949:Glucose Oxidase / Q000633:toxicity; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species; D024504:gamma-Tocopherol / Q000494:pharmacology*
D001786:Blood Glucose; D007328:Insulin; D017382:Reactive Oxygen Species; D024504:gamma-Tocopherol; D005949:Glucose Oxidase; D051057:Proto-Oncogene Proteins c-akt