IRS1 and Insulin resistance: Cannabinoid receptor gene (CNR1) is one of the important targets, Pei et al. (2018b) demonstrated that CNR1 expression was increased in HFD-induced mice with myocardial insulin resistance (decreased expression of IRS1/AMPKα/ACCA) and ERS, and further studies showed that knockdown of CNK1 ameliorated cardiac dysfunction and myocardial apoptosis in mice with DCM, and importantly, ameliorated insulin resistance and decreased ERS, and the in vitro studies further demonstrated that knockdown of CNK and activation of AMPKα ameliorated insulin resistance, suppressed ERS, and relieved DCM.