Oleate protects against palmitate-induced insulin resistance in L6 myotubes

Oleate has been shown to protect against palmitate-induced insulin resistance. The present Study investigates mechanisms involved in the interaction between oleate and palmitate on insulin-stimulated glucose uptake by L6 skeletal muscle cells. L6 myotubes Were Cultured for 6h with palmitate or oleate alone, and combinations of palmitate with oleate, with and without phosphatidylinositol 3-kinase (PI3-kinase) inhibition. Insulin-stimulated glucose uptake. measured by uptake of 2-deoxy-D-[H-3]glucose, was almost completely prevented by 30 mu M-palmitate. Cells incubated with oleate up to 750 mu mol/l maintained a significant increase in insulin-stimulated glucose uptake. Co-incubation of 50-300 mu M-oleate with 300 mu M-palmitate partially prevented the decrease in insulin-stimulated glucose uptake associated with palmitate. Adding the PI3-kinase inhibitors wortmannin (10(-7) mol/l) or LY294002 (25 mu mol/l) to 50 mu M-oleate plus 300 mu M-palmitate significantly reduced the beneficial effect of oleate against palmitate-induced insulin resistance, indicating that activation of PI3-kinase is involved in the protective effect of oleate. Thus, the prevention of palmitate-induced insulin resistance by oleate in L6 muscle cells is associated with the ability of oleate to maintain insulin signalling through PI3-kinase.