▁induced ▁apo pt osis . ▁Current ▁evidence ▁therefore ▁suggests ▁that ▁M AP 4 K 4 ▁has ▁a ▁mod ulating ▁effect ▁on ▁p 5 3 ▁induced ▁apo pt osis ▁in ▁the ▁J N K ▁signal ing ▁path way . ▁ ▁C lin ical ▁significance ▁ ▁Gl uc ose ▁u pt ake ▁and ▁ins ul in ▁function ▁ ▁M AP 4 K 4 ▁has ▁been ▁identified ▁to ▁be ▁involved ▁in ▁the ▁negative ▁reg ulation ▁of ▁ins ul in - dependent ▁gl uc ose ▁transport . ▁There ▁is ▁increasing ▁evidence ▁suggesting ▁cy tok ines ▁such ▁as ▁T NF - α ▁medi ate ▁bi ological ▁effects ▁ant agon istic ▁to ▁ins ul in ▁action ▁and ▁indu ce ▁infl amm ation ▁observed ▁in ▁ob es ity . ▁T NF - α ▁specifically ▁at ten u ates ▁the ▁signal ing ▁path way ▁initi ated ▁by ▁ins ul in ▁re cept ors , ▁reducing ▁the ▁amount ▁of ▁gl uc ose ▁transport ▁and ▁u pt ake ; ▁and ▁it ▁is ▁believed ▁that ▁M AP 4 K 4 ▁functions ▁as ▁an ▁up stream ▁signal ing ▁element ▁in ▁the ▁T NF - α ▁signal ing ▁cas cade . ▁ ▁A ▁recent ▁si R NA ▁screen ▁identified ▁the ▁invol vement ▁of ▁M AP 4 K 4 ▁in ▁the ▁reg ulation ▁of ▁the ▁gl uc ose ▁trans porter ▁GL UT 4 . ▁The ▁sil encing ▁of ▁M AP 4 K 4 ▁in ▁ad ip ocy tes ▁elev ated ▁the ▁expression ▁of ▁per ox is ome ▁pro l ifer ator - activ ated ▁re ceptor ▁y