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.