Inhibitory effect of fatty acids on glucose and insulin uptake in the perfused rat hindquarter

To elucidate the effects of fatty acids on the uptake of glucose and insulin in the muscle, the effects of oleic and palmitic acids on the uptake of glucose and insulin were investigated in perfused hind-quarters of rats. In the absence of insulin, glucose uptake in the hindquarter was slightly, but not significantly, decreased by the addition of oleic and palmitic acids. In the presence of 100 or 500 microU/ml insulin, glucose uptake in the hindquarter (243 +/- 58 or 282 +/- 65 mumol/30 min) was significantly decreased by the addition of 1000 microM oleic acid and 500 microM palmitic acid (175 +/- 50 or 207 +/- 47 mumol/30 min). The decrease in insulin uptake rate, although not significant at 500 microU/ml insulin, is of similar magnitude to the decrease in glucose uptake. In the presence of 1000 microU/ml insulin, glucose and insulin uptake was not significantly altered by the addition of fatty acids. These results indicate that fatty acids directly inhibit the muscular glucose uptake via the decrease in muscular insulin uptake at a physiological concentration of insulin.