Aldose reductase in the etiology of diabetic complications. 3. Neuropathy

Aldose reductase has been shown to be present in both autonomic and somatic nerves. Activation of this enzyme and the polyol pathway has been demonstrated in diabetic animal models to cause a range of biochemical, functional, and structural consequences that include the accumulation of sorbitol and fructose; axoglial dysjunction; paranodal demyelination; abnormalities in axonal transport, blood flow, and vascular permeability; and resistance to ischemic transmission of action potentials. These data provide an insight into the range of processes that if activated may either singly or in combination result in altered patterns of nerve function and structural alterations in diabetic neuropathy. In animal models of diabetes, it has been shown that inhibition of aldose reductase can modify these diabetes-induced changes. It is hoped that the results of large-scale controlled trials will provide clinical evidence to support these data.