The activity of aldose reductase is elevated in diabetic mouse heart

The importance of aldose reductase (AR) has been implicated in the pathogenesis of diabetic complications, although the alterations in the expression and activity of AR during hyperglycemia in the heart have not been well characterized. We investigated the expression and enzyme activity of AR in a murine diabetic model. Three weeks after the induction of hyperglycemia with streptozotocin, the level of AR mRNA was significantly reduced in the cardiac ventricles of BDF-1 mice. In contrast, the activity of AR was significantly elevated in the heart without any significant change in the protein level. In these mice, the level of cardiac thiobarbituric acid-reactive substances was unaltered, whereas the level of reduced glutathione (GSH) was significantly increased. Daily administration of insulin for 3 weeks completely normalized the level of AR mRNA and the enzyme activity. On the other hand, daily administration of an antioxidant, N-acetylcysteine significantly reduced the level of AR mRNA in the heart with a concomitant elevation in the enzyme activity. These results suggest that the activity of AR in the heart is affected by GSH dynamics. Augmented AR activity at the early stage of hyperglycemia may perturb glycolysis and affect cardiac performance.