Understanding Diabetic Neuropathy: Focus on Oxidative Stress

Figure 3

Four damaging pathways that can explain the detrimental effects of ROS in hyperglycaemia-induced diabetic neuropathy. The impaired glucose metabolism in diabetic condition causes an accumulation of glucose and glycolytic intermediates, which, instead of travel along glycolysis pathway, shunts to other metabolic or nonmetabolic pathways, resulting activation of the polyol pathway, hexosamine pathway, and AGE and PKC pathway. Superoxide inhibits glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity, which is proposed to be a reason causing accumulation of all the glycolytic intermediates. Pentose phosphate pathway (PPP pathway) is to generate NADPH, which is used in polyol pathway. GFAT: glutamine-fructose-6-phosphate aminotransferase; GAPDH: glyceraldehyde-3 phosphate dehydrogenase; PDH: pyruvate dehydrogenase.