In DIO mice, high levels of BCAAs/BCKAs suppressed Akt2 activation and promoted Akt2 ubiquitin–proteasome-dependent degradation through the mTORC2 pathway, depending on the E3 ligase Mul1, finally leading to serious hepatic glucose and lipid metabolic disorder and severe insulin resistance in the liver [80]. This evidence concerns the gene AKT2 and Insulin resistance.