Figure 8. Proposed scheme for the mechanism that regulates high glucose-induced injury in CMECs.

High glucose inhibits Akt activation, which subsequently activates FoxO3a and directly stimulates ROS formation. Activated FoxO3a translocates to nucleus and regulates target genes, which suppresses ROS accumulation in CMECs. In parallel, FoxO3a increased the pro-apoptotic protein Bim and decreased the expression of anti-apoptotic proteins Bcl-xL, which trigger the apoptosis of CMECs. Accordingly, FoxO3a plays a central role in high glucose induced ROS formation and apoptosis in CMECs.