Aldose reductase (AR; EC 18.104.22.168) is a NADPH-dependent oxidoreductase and considered the key enzyme in the polyol pathway. It catalyzes the reduction of a variety of aldehydes and carbonyls, including monosaccharides, and is primarily known for the conversion of glucose into sorbitol. During states of hyperglycemia, the polyol pathway has increased activity, resulting in elevated sorbitol levels. Increases in sorbitol concentrations result in cellular and organ injury and in the decrease of myo-inositol in the peripheral nerves. When myo-inositol is decreased, there is a resulting decrease in Na+/K+ ATPase activity, which is essential for nerve conduction. Additionally, increased polyol pathway activity and the overutilization of NADPH by AR may affect a number of other homeostatic mechanisms: NADPH depletion results in decreased nitric oxide (NO) and reduced glutathione production. Inhibition of this enzyme causes a decrease in the accumulation of sorbitol in the cells, and may serve possible treatments for diabetic neuropathy.
 K.E. Schemmel et al . Aldose reductase inhibitors in the treatment of diabetic peripheral neuropathy: a review. J. Diabetes Complications. 2010, 24, 354-360.