To better understand the direct impact of NPs on cardiac tissues in an in vivo DIO model and to determine their functional significance, we used DIO mice with continuous subcutaneous ANP treatment to investigate whether or not exogenous ANP treatment ameliorates insulin resistance in cardiac tissues, similar to observations in adipose and hepatic tissues [6], leading to cardioprotection during IRI through the restoration of Akt signaling. Here, AKT1 is linked to Insulin resistance.