Increased Aldose Reductase Activity

The aldose reductase pathway has been extensively studied because of the presence of the enzyme in the retina, kidney, and nerves. These are all targets for the long-term complications and would present a unified model for the damage caused by chronic hyperglycemia. The enzyme increases its activity in the presence of high blood glucose levels and causes increased levels of sorbitol. Sorbitol dehydrogenase metabolizes the sorbitol that is then postulated to lead to other metabolic changes that can cause neuropathy and retinopathy. This pathway has been best studied in relation to diabetic neuropathy (8). Despite this understanding of the possible underlying role for this mechanism, trials of aldose reductase inhibitors in slowing down the development or progression of retinopathy and neuropathy have not been very effective.

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