Heavy metal ion-induced insulin-mimetic signaling

The serines threonine kinase Akt is a mediator of insulin effects on target cells and, as such, is a major regulator of fuel metabolism. Akt was demonstrated to be activated in a phosphoinositide 3'- kinase-dependent fashion by stressful stimuli, including reactive oxygen species (ROS) and certain heavy metal ions. This minireview focuses on activation of the PI3K/Akt signaling cascade by exposure of cells to transition metal ions, such as Cu(II), Zn(II) or Ni(II), and discusses potential mechanisms of Akt activation and the role of ROS therein and consequences for signaling processes downstream of Akt, including modulation of FoxO-family transcription factors. In addition, we speculate on the significance of these findings with respect to processes with which FoxO proteins are known to be involved, i.e. stress-induced senescence and selenium homeostasis.