Review Article Hypoxia in Diabetic Kidneys

Copyright © 2014 Y. Takiyama and M. Haneda.This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Diabetic nephropathy (DN) is now a leading cause of end-stage renal disease. In addition, DN accounts for the increased mortality in type 1 and type 2 diabetes, and then patients withoutDN achieve long-term survival compatible with general population.Hypoxia represents an early event in the development and progression of DN, and hypoxia-inducible factor- (HIF-) 1 mediates themetabolic responses to renal hypoxia. Diabetes induces the “fraternal twins ” of hypoxia, that is, pseudohypoxia and hypoxia. The kidneys are susceptible to hyperoxia because they accept 20 % of the cardiac output. Therefore, the kidneys have specific vasculature to avoid hyperoxia, that is, AVoxygen shunting.TheNAD-dependent histone deacetylases (HDACs) sirtuins are sevenmammalian proteins, SIRTs 1–7, which are known to modulate longevity and metabolism. Recent studies demonstrated that some isoforms of sirtuins inhibit the activation of HIF by deacetylation or noncatalyzing effects. The kidneys, which have a vascular system that protects them against hyperoxia, unfortunately experience extraordinary hypernutrition today. Then, an unexpected overload of glucose augments the oxygen consumption, which ironically results in hypoxia. This review highlights the primary role of HIF in diabetic kidneys for the metabolic adaptation to diabetes-induced hypoxia. 1. Hypoxia in Diabetic Kidne