Consistent with the development of mTOR inhibitors as a glucose-lowering agent, mTOR is over-activated in high-fat diet (HFD)-induced obese rodents and induces insulin resistance in the liver and muscle10, 11; whereas the downregulation of mTOR signaling, or the deletion of S6 kinase (S6K), the crucial effector of mTOR signaling, is sufficient to enhance insulin sensitivity in rodents12, 13. The gene discussed is INS; the disease is Insulin resistance.