Evidence that the islet is uniquely at risk for oxidative damage.
The concept that the islet is unusually at risk for damage by pro-oxidant forces is not a new one (Fig. 3). Oxidative phosphorylation during anaerobic glycolysis generates reactive oxygen species (ROS), a process that might become excessive in hyperglycemic states (15). The following are metabolic pathways that excess glucose might be shunted into when it accumulates beyond the levels that glycolytic enzymes can handle and that can form ROS: glycosylation (Schiff reaction) (16), glucose autoxidation (17,18), and the glucosamine pathway (19). ROS that might be formed include superoxide, hydrogen peroxide, nitric oxide, and hydroxyl radicals. Among these, the hydroxyl radical is the most toxic because it easily passes through membrane barriers to the cell’s nucleus and strongly reacts mutagenically with DNA.