Thesefindings fitted with the current model whereby excess nutrient (glucose andFree Fatty Acids) and chronic hyperinsulinemia downregulate insulin response intarget tissues by hyperactivating S6K, that in turn leads to serinephosphorylation and proteasomal degradation of the major insulin transducerIRS-1 [21]. The gene discussed is INS; the disease is Hyperinsulinemia.