〔Abstract〕 Objective To investigate the effect of HUA on insulin resistance in cardiomyocytes and hyperuricemic mouse model. Methods We exposed primary cardiomyocytes and a rat cardiomyocyte cell line H9 c2 cardiomyocytes to HUA,then quantified glucose uptake with a fluorescent glucose analog, 2-NBDG,after insulin challenge and detected reactive oxygen species(ROS) production.Western blot analysis was used to examine the levels of phosphorylated insulin receptor substrate 1(IRS1,Ser307) and phospho-Akt(Ser473).We monitored the impact of HUA on insulin resistance, insulin signaling, phospho-IRS1(Ser307) and phospho-Akt levels in myocardial tissue of an acute hyperuricemia mouse model established by potassium oxonate treatment.Results HUA inhibited insulin-induced glucose uptake in H9 c2 cardiomyocytes. It increased ROS production,pretreatment with N-acetyl-L-cysteine(NAC),a ROS scavenger,reversed HUA-inhibited glucose uptake induced by insulin. HUA exposure directly increased the phospho-IRS1(Ser307) response to insulin and inhibited that of phospho-Akt in H9 C2 cardiomyocytes,which was blocked by NAC. Furthermore,the acute hyperuricemic mice model showed impaired glucose tolerance and insulin tolerance accompanied by increased phospho-IRS1(Ser307) and inhibited phospho-Akt response to insulin in myocardial tissues.Conclusion HUA inhibits insulin signaling and induces insulin resistance in cardiomyocytes in vitro and in vivo, which is a novel potential mechanism of hyperuricemic-related cardiovascular disease.