Interestingly, silencing the expression of RARα and RXRα in cardiomyocytes promoted the activation of the JNK pathway in vitro [187] and in vivo (in the hearts of RARαKO and RXRαKO mice) [188], suggesting that impaired RAR/RXR signaling and oxidative stress/the JNK pathway form a vicious circle, which may significantly contribute to diabetes-induced cardiac remodeling (Figure 4). This evidence concerns the gene MAPK8 and diabetes mellitus.