PTEN and diabetes mellitus: Decreased NO• production in diabetes is attributed to diminished eNOS expression [99], overexpression of negative regulators of eNOS activity [i.e., the membrane-associated scaffolding protein caveolin-1 (Cav-1) and phosphatase and tensin homolog (PTEN)] [103–105], substrate deficiency for NOSs [due to increased arginase activity and decreased l-arginine availability [106, 107]], eNOS uncoupling [due to elevated ROS, oxidation of tetrahydrobiopterin (BH4), l-arginine depletion, and accumulation of methylarginines] resulting in superoxide anion instead of NO production [108].