Thus, besides impaired hepatic insulin signaling, the ADMA-mediated inhibition of glucose uptake by the skeletal muscles – in part dependent on the blockade of vascular endothelial-type NO synthase (eNOS) and consequently blunted muscular perfusion under hyperinsulinemic conditions [41-43] – might have contributed to the relations between DDAH-2 polymorphism and diabetes incidence or IR [22], providing also a mechanistic explanation for our findings. The gene discussed is DDAH2; the disease is diabetes mellitus.