Treatment with trilobatin prevented palmitate-induced insulin resistance by enhancing glucose uptake and the phosphorylation of insulin resistance substrate 1 (IRS1) and protein Kinase B, (PKB/AKT), recovered the translocation of GLUT4 from cytoplasm to membrane, but preincubation with LY294002, an inhibitor of PI3K, blocked the effects of trilobatin on glucose uptake and the distribution of GLUT4 in C2C12 myotubes. Here, IRS1 is linked to Insulin resistance.