PRRT2 and Hyperglycemia: Hyperglycemia determines directly (through an increase in diacylglycerol) or indirectly (through the oxidative stress and the increase of ROS) increased protein-kinase C (PKC) signaling, which can upregulate NF-κB and downregulate eNOS [44], stimulate the production of cytokines, the extracellular matrix, the fibrinolytic inhibitor plasminogen activator inhibitor (PAI-1), the vasoconstrictor endothelin-1 and VEGF.