Hypoxia in Obesity and Diabetes: Potential Therapeutic Effects of Hyperoxia and Nitrate

Figure 3

Hypoxia-inducible factor-1α (HIF-1α) degradation/stabilization. Inhibition of prolyl hydroxylase domain (PHD) enzymes by hypoxia and nitric oxide (NO) leads to stabilization of HIF-1α. Hypoxia upregulates the arginase enzyme; thus, the substrate of NO synthase (NOS), arginine, is reduced and NO production is decreased. Furthermore, hypoxia can induce production of ROS (superoxide anion). The bioavailability of ROS and NO is regulated by each other. HIF-1α upregulates inducible NOS (iNOS), which produces NO. NO inhibits PHD and stabilizes HIF-1α; NO can also contribute to angiogenesis through vascular endothelial growth factor (VEGF), which is upregulated by HIF-1α. Asn: asparagine; Pro: proline; pVHL: Von Hippel-Lindau tumor suppressor protein.