Others provided a role for PAK upstream of p53 [71,72], thus PAK signaling in T2DM may activate p53 directly, or indirectly via MDM2, or through a cell stress pathway, such as oxidative stress or stress associated MAPK like p38/JNK [73], thereby inducing apoptosis, impeding cell cycle progression, and subsequently reducing beta cell mass. This evidence concerns the gene MAPK8 and type 2 diabetes mellitus.