Exogenous triacylglycerol inhibits insulin-stimulated glucose transport in L6 muscle cells in vitro.

This study tested the hypothesis using cultured L6 myocytes that insulin resistance in muscle may be the consequence of triacylglycerol accretion in the tissue itself. Exposure of L6 myocytes to triacylglycerol for 4 hours resulted in significant transfer of lipid into the cells compared to control cells treated for only 5 min. Insulin-stimulated 2-deoxyglucose uptake in L6 myocytes was reduced when the cells were preloaded with triacylglycerol. Insulin-independent and insulin-stimulated 2-deoxyglucose uptake were inhibited by cytochalasin B, indicating that both were transporter-mediated. Diacylglycerol mimicked insulin action by increasing 2-deoxyglucose uptake and this was also reduced by triacylglycerol preloading, suggesting that the effect was not mediated at the insulin receptor. Thus, triacylglycerol may exert a direct effect on muscle cell insulin sensitivity possibly at the level of diacylglycerol second messenger pathway.