Effect of Inflammation on Ketoisocaproic Acid Induced Insulin Resistance In Skeletal Muscle Cells

Branched-chain amino acids (BCAAs) have displayed metabolic benefits, and play a role in muscle protein synthesis. However, elevated levels of BCAAs and their metabolites have been linked to the pathogenesis of insulin resistance and type 2 diabetes mellitus. It has been demonstrated in my lab that -ketoisocaproic acid (KIC), a metabolite of leucine, inhibited insulin-stimulated glucose uptake, but is converted back to leucine in order to do so. Inflammation, a feature of insulin resistance may modulate the effects of amino acids and their metabolites on insulin action. Thus, I analyzed whether or not there was an additive effect of KIC and inflammation on insulin-stimulated glucose transport in L6 myotubes. Results emphasize previous findings, that even in the presence of inflammation, KIC is converted back to leucine to inhibit insulin-stimulated glucose uptake, suggesting that interventions altering BCAA pathway flux may help in the management/prevention of insulin resistance.