NOS3 and hyperinsulinemic hypoglycemia, familial, 4: In an animal model of IGF-1 deficiency, which usually exhibited increased reactive oxygen species (ROS) production and decreased NO bioavailability (Csiszar et al., 2008), IGF-1 treatment up-regulates endothelial nitric oxide synthase (eNOS) and increases NO bioavailability (Cittadini et al., 2009; Sonntag et al., 2013).