Figure 4.

Link between glucose-derived carbonyl stress and the Warburg effect as a new unifying hypothesis of diabetic complications [5,43], alternative to the overproduction of mitochondrial reactive oxygen species (ROS) induced by hyperglycemia. Refer to the main text for detailed description and references. Dashed arrows/lines/box = subsequent processes (or “second hit”) participating in the progression of diabetic complications. TCA = tricarboxylic acid; MGO = methylglyoxal; AGE = advanced glycation end product; PKC = protein kinase C; PHDs = prolyl hydroxylase domain enzymes; HIF-1α = hypoxia-inducible factor-1α.; HIFs = hypoxia-inducible factors.