Oxidative stress-induced insulin resistance in skeletal muscle cells is ameliorated by gamma-tocopherol treatment.

Oxidative stress-induced reactive oxygen species are associated with the clinical manifestation of insulin resistance. Evidence suggests that antioxidant treatment may reduce this incidence. 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). Insulin sensitivity in L6 myotubes was assessed by 2-deoxy- d-[3H]-glucose uptake. The phosphorylation of distal insulin signaling proteins Akt and the Akt substrate AS160 were determined by western blot. One hour treatment with 100 mU/ml GO decreased insulin-stimulated glucose uptake (P < 0.001). Pre-treatment with GT either partially (100 µM) or completely (200 µM) 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 µM GT increased insulin-stimulated phosphorylation of these key signaling proteins ( P < 0.05). High-dose (200 µM) GT treatment ameliorated oxidative stress-induced insulin resistance in cultured rat L6 skeletal muscle cells. [ABSTRACT FROM AUTHOR]