One of the well described negative feedback loops takes place in response to overnutrition‐induced constitutive mTORC1 activation which leads to inhibitory phosphorylations on IRS‐1 by S6K1.[20] mTORC1 itself also phosphorylates IRS1 to promote its proteasome‐dependent degradation.[21]. The gene discussed is IRS1; the disease is overnutrition.