PRRT2 and diabetes mellitus: The various possible sources for the overproduction of ROS in diabetes include (Figure 1): (1) Activation of the polyol pathway leading to the accumulation of sorbitol and fructose, NADPH redox imbalances, and changes in signal transduction; (2) The increased flux of the hexosamine pathway; (3) Increased protein kinase C (PKC) activity and subsequent cascades of stress; (4) The non-enzymatic glycation of proteins generating advanced glycation end-products (AGEs); and (5) Activation of the small GTPase Rho and its target, Rho-kinase (ROCK).