British Journal of Nutrition

Full Papers

Molecular Nutrition

Oleate protects against palmitate-induced insulin resistance in L6 myotubes

Dan Gaoa1, Helen R. Griffithsa1 c1 and Clifford J. Baileya1

a1 School of Life and Health Sciences, Aston University, Birmingham B4 7ET, UK

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.

(Received February 12 2009)

(Revised April 29 2009)

(Accepted May 26 2009)

(Online publication July 22 2009)

Correspondence:

c1 Corresponding author: Dr Helen R. Griffiths, fax +44 121 359 0572, email h.r.griffiths@aston.ac.uk

Footnotes

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