Effects of individual fatty acids on glucose uptake and glycogen synthesisin soleus muscle in vitro

Soleus muscle strips from Wistar rats were preincubated with palmitate in v itro before the determination of insulin-mediated glucose metabolism in fat ty acid-free medium. Palmitate decreased insulin-stimulated glycogen synthe sis to 51% of control in a time- (0-6 h) and concentration-dependent (0-2 m M) manner. Basal and insulin-stimulated glucose transport/phosphorylation a lso decreased with time, but the decrease occurred after the effect on glyc ogen synthesis. Preincubation with 1 mM palmitate, oleate, linoleate, or li nolenate for 4 h impaired glycogen synthesis stimulated with a submaximal p hysiological insulin concentration (300 mu U/ml) to 50-60% of the control r esponse, and this reduction was associated with impaired insulin-stimulated phosphorylation of protein kinase B (PKB). Preincubation with different fa tty acids (all 1 mM for 4 h) had varying effects on insulin-stimulated gluc ose transport/ phosphorylation, which was decreased by oleate and linoleate , whereas palmitate and linolenate had little effect. Across groups, the ra tes of glucose transport/ phosphorylation correlated with the intramuscular long-chain acyl-CoA content. The similar effects of individual fatty acids on glycogen synthesis but different effects on insulin-stimulated glucose transport/ phosphorylation provide evidence that lipids may interact with t hese two pathways via different mechanisms.