Insulin increases FA uptake and esterification but reduces lipid utilization in isolated contracting muscle

We examined the effect of insulin on the synthesis and degradation of muscl e lipid pools [phospholipid (PL), diacylglycerol (DG), triacylglycerol (TG) ] and palmitate oxidation in isolated resting and contracting (20 tetani/mi n) soleus muscles. Lipid metabolism was monitored using the previously defi ned pulse-chase procedure. At rest, insulin significantly increased total p almitate uptake into soleus muscle (+49%, P < 0.05), corresponding to enhan ced DG (+60%, P < 0.05) and TG (+61%, P < 0.05) esterification, but blunted palmitate oxidation (-38%, P < 0.05) and TG hydrolysis (-34%, P < 0.05). D uring muscle contraction, when total palmitate uptake was increased, insuli n further enhanced uptake (+21%, P < 0.05) and esterification of fatty acid s (FA) to PL (+73%, P < 0.05), DG (+ 19%, P < 0.05), and TG (+ 161%, P < 0. 01). Despite a profound shift in the relative partitioning of FA away from esterification. and toward oxidation during contraction, the increase in pa lmitate oxidation and TG hydrolysis was significantly blunted by insulin [o xidation, -24% (P = 0.05); hydrolysis, -83% (P < 0.01)]. The effects of ins ulin on FA esterification (stimulation) and oxidation (inhibition) during c ontraction were reduced in the presence of the phosphatidylinositol 3-kinas e inhibitor LY-294002. In summary, the effects of insulin and contraction o n palmitate uptake and esterification are additive, while insulin opposes t he stimulatory effect of contraction on FA oxidation and TG hydrolysis. Ins ulin's modulatory effects on muscle FA metabolism during contraction are me diated at least in part through phosphatidylinositol 3-kinase.