MAPK3 and Insulin resistance: While dysregulation of these proteins by the insulin signaling pathway causes mitochondrial fragmentation and cellular dysfunction and failure.[21] Under high glucose stimulation, the activation of ERK1/2 and ROCK1 induces phosphorylation of Drp1, down-regulation of OPA1, and loss of Mfn2, leading to mitochondrial fission and ROS generation, eventually triggering mitochondrial dysfunction and myocardial insulin resistance.[22] The role of mitochondrial dynamics in regulating the insulin resistance mechanisms requires further exploration.