In this study, we found that administration of eNOS inhibitor L-NMMA significantly and partially abolished the beneficial effects of CYP2J3 gene delivery on insulin resistance induced by fructose intake, which is supported by the results of recent study that increased NO availability attenuates high fat diet induced metabolic alterations and gene expression associated with insulin resistance[23], and its possible mechanism is associated with inhibited IRS-1/PI3K/AKT and AMPK signalling pathways. Here, IRS1 is linked to Insulin resistance.