Akt2 knockout mitigates chronic iNOS inhibition-induced cardiomyocyte atrophy and contractile dysfunction despite persistent insulin resistance

► iNOS inhibition promotes insulin resistance, anomalies in cardiac contractile function and intracellular Ca2+ handling. ► Akt2 knockout attenuates iNOS inhibition-induced cardiac contractile and intracellular Ca2+ derangement. ► Akt2 knockout promotes intracellular Ca2+ regulatory proteins SERCA2a and phospholamban phosphorylation. ► Neither iNOS inhibition nor Akt2 knockout significantly affects post-insulin receptor and stress signaling.