Different Pathogenic Mechanisms Reflect A Single

Although specific inhibitors of aldose reductase activity, AGE formation, and PKC activation each ameliorate various diabetes-induced abnormalities in animal models, there has been no apparent common element linking the four mechanisms of hyper-glycemia-induced damage discussed in the preceding section (88,107-110). This issue has now been resolved by the recent discovery that each of the four different pathogenic mechanisms reflects a single hyperglycemia-induced process: overproduction of superoxide by the mitochondrial electron transport chain (111,112).

Hyperglycemia increases reactive oxygen species (ROS) production inside cultured bovine aortic endothelial cells (113). To understand how this occurs, a brief overview

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