Aldose reductase is an enzyme that catalyzes one of the steps in the sorbitol (polyol) pathway that is responsible for fructose formation from glucose. In hyperglycemic states, aldose reductase activity increases in the tissues that are not insulin sensitive to break down glucose, increasing sorbitol levels. As sorbitol does not diffuse through cell membranes easily, it will accumulate in the cell resulting in changes in osmotic pressure that cause tissue damage. This pathway potentially plays a role in complications of diabetes such as diabetic retinopathy and diabetic neuropathy.
Using aldose reductase inhibitors (ARIs) to decrease that sorbitol flux through the polyol pathway could be a target for the prevention and management of the complications of diabetes. However, generally, the results of using aldose reductase inhibitors in clinical trials have been disappointing. The potential for these drugs is still considered to be there and work is continuing.
eg Epalrestat, Sorbinil, Ranirestat
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