PRRT2 and Hyperglycemia: Hyperglycemia is one of the main triggers of these maladaptive processes, including the impairment of insulin signaling, which leads to plasmalemmal depletion of the glucose transporter (GLUT4), changes in free fatty acid (FA) oxidation, protein kinase C (PKC) activation, increased pathways of polyol and hexosamine, and production of advanced glycation end products (AGE) and reactive oxygen species (ROS) (Figure 1).