INS and metabolic disease: These processes, in turn, promote protein synthesis and antagonize protein degradation.135 Further, PRAS40 and mTOR also exerts negative feedbacks on proximal insulin signaling, PRAS40 knockdown significantly decreases Akt phosphorylation, mTORC1 binds and inhibits INSR by inducing destabilization of IRS1.28 The signaling system of IR are multifactorial including different metabolic pathways, such as glucose, lipid, and protein, identifying new molecules will be crucial to unraveling more effective treatment of IR and associated metabolic diseases.