ABSTRACT
The excessive production of reactive-oxygen species has been demonstrated in experimental diabetes and been linked to both peripheral-nerve dysfunction (64, 76) and microvascular disease (28). It has been postulated that this is the mechanism 320for many diabetic complications (31). This theory has attracted a great deal of attention recently, because several adverse consequences of chronic hyperglycemia — the formation of advanced glycation end products (74), activation of the aldose reductase pathway (37), endothelial dysfunction (94), peroxynitrite formation (28), lipid peroxidation (64), activation of vascular NADPH oxidases (37), mitochondrial dysfunction (74), and programmed cell death (85) — have been linked to oxidative stress in animal models. Possible interactions between these biochemical mechanisms have been reviewed in depth elsewhere (31, 74). The present review pertains mainly to oxidative stress in human diabetes and will focus on peripheral nerve and beta-cell dysfunction.
