Fig. (1) Hypothetical representation of PI3K/AKT/PTEN signaling in pancreatic β-cells is shown, which modulate NOXs-derived reactive oxygen species (ROS) generation. The NOXs sense persistent hyperglycemia, DNA stress, hypoxia, and so on. Uncontrolled generation of ROS might then contribute to the various pathway signaling. Examples of molecules known to act on the regulatory pathway are shown. Arrowhead means stimulation whereas hammerhead represents inhibition. Note that some critical pathways have been omitted for clarity.