FIG. 7.

The polyol pathway contributes to cardiomyocyte damage in diabetes. Hyperglycemia stimulates flux through the polyol pathway, comprising aldose reductase and sorbitol dehydrogenase. Metabolic conversion of glucose to sorbitol by aldose reductase is usually followed by further conversion of sorbitol to fructose. In diabetes, sorbitol accumulates intracellularly and is not cell permeable. Accumulation of sorbitol causes osmotic stress, and NADPH depletion results in oxidative stress and the generation of ROS, leading to cell damage.