Palmitate oxidation rate and action on glycogen synthase in myoblasts frominsulin-resistant subjects

Elevated plasma lipid and nonesterified fatty acid concentrations reduce in sulin-mediated glucose disposal in skeletal muscle. Cultured myoblasts from 21 subjects were studied for rates of palmitate oxidation and the effect o f palmitate on glycogen synthase activity at the end of an 18-h incubation in serum- and glucose-free media. Oxidation rates of 40 mu M palmitate in c ultured myoblasts correlated with the fasting glucose (r = 0.71, P = 0.001) , log fasting insulin (r = 0.52, P = 0.03), and insulin-mediated glucose st orage rate (r = -0.50, P = 0.04) of the muscle donors. Myoblast glycogen sy nthase activity can be regulated by 240 mu M palmitate, but the changes are associated with the basal respiratory quotient and not with the insulin re sistance of the muscle donor. These results indicate that myoblasts produci ng elevated palmitate oxidation rates in vitro can be used to identify skel etal muscle abnormalities which are primary contributors to insulin resista nce in vivo. Effects of 240 mu M palmitate on myoblast glycogen synthase ac tivity appear to be mechanistically different from the relationship between myoblast palmitate oxidation rates and insulin resistance of the muscle do nor.