Leucine promotes glucose uptake in skeletal muscles of rats

Abstract

Soleus muscles isolated from normal rats were incubated to evaluate whether or not leucine promotes glucose uptake under insulin-free conditions, using a labeled 2-deoxyglucose uptake assay. Glucose uptake was promoted by 2 mM leucine. A metabolite of leucine, α-ketoisocaproic acid (α-KIC), also exhibited a similar stimulatory effect, although this was not as potent as leucine. Stimulation of glucose uptake by leucine was completely canceled by pre-treatment with either 10 μM LY294002, a specific inhibitor of phosphatidylinositol 3-kinase (PI3-kinase), or 6 μM GF109203X, a specific inhibitor of protein kinase C (PKC). No significant change was observed by pre-treatment with 1 μM rapamycin, a specific inhibitor of mammalian target of rapamycin (mTOR). These results suggest that leucine stimulates glucose transport in skeletal muscle via PI3-kinase and PKC pathways independently of the mammalian target of mTOR. They also suggest that leucine stimulates glucose transport by an insulin-independent mechanism.