NOS3 and Hyperglycemia: Specifically, metabolic abnormalities of DM, especially hyperglycemia and hyperlipidemia, can activate NADPH oxidases (NOXs) and endothelial Nitric Oxide Synthase (eNOS), increase advanced glycation end-products (AGE), and interrupt the polyol pathway as well as the mitochondrial respiratory chain, to impinge on oxidative stress (19).