Early diabetic neuropathy: Triggers and mechanisms

Figure 6 Hyperglycemia, derangement of cell metabolism and oxidative/nitrosative stress. Hyperglycemia associates with accumulation of fructose-6-phosphate and hexosamine pathway (1) to N-acetylglucosamine, accumulation of dihydroxyacetone phosphate and associated activation of PKC (2), activation of polyol sugar pathway (3), and glucose autoxidation and non-enzymatic protein glycation (4). These metabolic events are either regular physiologically important components cell metabolism (1, 2 and 3) or are normally under strict control of intrinsic intracellular defense mechanisms (4). However, under conditions of chronic hyperglycemia activation of these pathways leads to a global derangement of the cell and tissue homeostasis, which culminates in an uncontrolled cascade of abnormal protein modifications, oxidative/nitrosative stress and pro-inflammatory conditions.