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Oleate protects against palmitate-induced insulin resistance in L6 myotubes

  • Dan Gao (a1), Helen R. Griffiths (a1) and Clifford J. Bailey (a1)
  • DOI: http://dx.doi.org/10.1017/S0007114509990948
  • Published online: 22 July 2009
Abstract

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.

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*Corresponding author: Dr Helen R. Griffiths, fax +44 121 359 0572, email h.r.griffiths@aston.ac.uk
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