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 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 microm-palmitate. Cells incubated with oleate up to 750 micromol/l maintained a significant increase in insulin-stimulated glucose uptake. Co-incubation of 50-300 microm-oleate with 300 microm-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 micromol/l) to 50 microm-oleate plus 300 microm-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.
Gao
Dan
D
School of Life and Health Sciences, Aston University, Birmingham, UK.
Griffiths
Helen R
HR
Bailey
Clifford J
CJ
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D003847:Deoxyglucose / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007333:Insulin Resistance / Q000502:physiology*; D009025:Morpholines / Q000494:pharmacology; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D032448:Myoblasts, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D019301:Oleic Acid / Q000494:pharmacology*; D010168:Palmitates / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051381:Rats; D000077191:Wortmannin
D000730:Androstadienes; D002867:Chromones; D003847:Deoxyglucose; D004791:Enzyme Inhibitors; D009025:Morpholines; D019301:Oleic Acid; D010168:Palmitates; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D000077191:Wortmannin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one