While some evidence indicates that oxidative stress typically activates Nrf2 through Keap1 oxidation-induced nuclear translocation (Bellezza et al., 2018), our study revealed a paradoxical suppression of Nrf2 signaling in diabetic cardiomyopathy, with HG inhibiting Nrf2 protein expression in cardiomyocytes. Here, KEAP1 is linked to diabetic cardiomyopathy.