Insulin and nutrients activate hepatic p70 S6 kinase (S6K1) to regulate protein synthesis.
Paradoxically, activation of S6K1 also leads to the development of insulin resistance. In this
study, we investigated the effect of TRB3, which acts as an endogenous inhibitor of Akt, on
S6K1 activity in vitro and in vivo. In cultured cells, overexpression of TRB3 completely
inhibited insulin-stimulated S6K1 activation by mammalian target of rapamycin, whereas
knockdown of endogenous TRB3 increased both basal and insulin-stimulated activity. In …