ELEVATED FREE FATTY-ACID LEVELS INHIBIT GLUCOSE PHOSPHORYLATION IN SLOW-TWITCH RAT SKELETAL-MUSCLE

The effect of increased free fatty acid concentrations on glucose meta bolism in rat skeletal muscle was investigated at several different st eps in glucose metabolism including glucose transport, glucose phospho rylation, glucose oxidation and glycogen synthesis. In isolated soleus (slow-twitch) muscles, insulin-stimulated (100 mu U ml(-1)) glucose p hosphorylation, but not glucose transport, was inhibited by 26 and 22% in the presence of 1.0 and 2.0 mM oleate, respectively (P < 0.01). Re gardless of oleate concentration (0.3 or 2.0 mM), insulin-stimulated g lucose 6-phosphate levels were elevated to the same extent over the no n-insulin-stimulated levels in soleus muscles (P < 0.01). Insulin-stim ulated glucose oxidation was inhibited by 44% in soleus muscles expose d to 2.0 mM oleate (P < 0.05), whereas the rate of glucose incorporati on into glycogen was not altered. In insulin-stimulated epitrochlearis (fast-twitch) muscles, elevated concentrations of oleate had no effec t on the rates of glucose transport or glucose phosphorylation, or on the level of glucose 6-phosphate. These data suggest that increased fr ee fatty acid availability decreases glucose utilization by selectivel y inhibiting glucose phosphorylation and oxidation in slow-twitch, but not fast-twitch skeletal muscle.