Review Article
Modulating DDAH/NOS Pathway to Discover Vasoprotective Insulin Sensitizers
Figure 2
The DDAH/ADMA/NOS pathway and insulin sensitivity. The expression of dimethylarginine dimethylaminohydrolase (DDAH) is upregulated by existing insulin sensitizers such as metformin and pioglitazone or new chemical entities (NCEs). Upregulated DDAH reduces the level of its substrate asymmetric dimethylarginine (ADMA) and increases nitric oxide (NO) production. NO can directly target insulin-responsive tissues to enhance insulin sensitivity. Increased glucose uptake reduces oxidative stress and in turn alleviates DDAH expression.