a1 School of Life and Health Sciences, Aston University, Birmingham B4 7ET, UK
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 6 h 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-[3H]glucose, was almost completely prevented by 300 μm-palmitate. Cells incubated with oleate up to 750 μmol/l maintained a significant increase in insulin-stimulated glucose uptake. Co-incubation of 50–300 μm-oleate with 300 μm-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 μmol/l) to 50 μm-oleate plus 300 μm-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.
(Received February 12 2009)
(Revised April 29 2009)
(Accepted May 26 2009)
(Online publication July 22 2009)
Abbreviations: BSA, bovine serum albumin; DMEM, Dulbecco's modified Eagle's medium; FBS, fetal bovine serum; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; PI3-kinase, phosphatidylinositol 3-kinase