TRB-3 (tribbles 3), also called NIPK (neuronal cell death-inducible protein kinase) disrupts insulin signaling by binding directly to Akt kinases and blocking their activation. TRB3 binds to ATF4, inhibiting its transcriptional activation activity, and regulates activation of MAP kinases. In the liver, TRB-3 is a target for PPAR-alpha. Amounts of TRB3 RNA and protein are higher in livers of diabetic mice compared with those in wildtype mice. TRB3 contributes to insulin resistance in individuals with susceptibility to type II diabetes. Highest expression of TRB-3 is in liver, pancreas, peripheral blood leukocytes and bone marrow.