Abstract:
Excess plasma free fatty acids (FFA) are correlated with insulin resistance and are
a risk factor for the development of type 2 diabetes. In this study we examined the effect
of the polyphenol resveratrol on FF A-induced insulin resistance in skeletal muscle cells
and the mechanisms involved. Incubation of L6 myotubes with the FF A palmitate
significantly decreased the insulin-stimulated glucqse uptake. Importantly, the effect of
palmitate was ameliorated by resveratrol. Palmitate significantly increased serine
phosphorylation of IRS..; 1 and reduced insulin-stimulated Akt phosphorylation, an effect
that was abolished by resveratrol. We then investigated the effect of palmitate and
resveratrol on the expression and phosphorylation of JNK, mTOR, p70-S6K, and AMPK
kinases. The results demonstrated that our treatments had no effect on the expression of
these proteins. However, palmitate increased the phosphorylation of mTOR and p70-
S6K, whereas resveratrol abolished this effect and increased the phosphorylation of
AMPK. Furthermore, all effects of resveratrol were abolished with sirtuin inhibitors,
sirtinol and nicotinamide. These results indicate that resveratrol ameliorated FF A-induced
insulin resistance by regulating mTOR and p70-S6K phosphorylation in skeletal muscle
cells, through a mechanism involving sirtuins.
