Crucial role of aldose reductase activity and plasma glucose level in sorbitol accumulation in erythrocytes from diabetic patients

Increased sorbitol levels have been demonstrated in tissues of diabetic patients. Although tissue sorbitol levels correlate with plasma glucose levels, a large variability in sorbitol levels has been observed among diabetic patients with similar plasma glucose levels. This variability in tissue sorbitol levels may be due to differences in the activity of Aldose Reductase, the Enzyme that converts glucose to sorbitol. In this study, we isolated Aldose Reductase from erythrocytes of 31 diabetic patients and 6 nondiabetic control subjects, measured its activity, and compared it to simultaneously measured erythrocyte sorbitol levels. The activity of erythrocyte Aldose Reductase was increased in diabetic patients compared with control subjects (28.1 +/- 1.4 vs. 22.4 +/- 1.7 nmol.min-1.g-1 Hb, P less than 0.05), but there was an approximately threefold variation in Aldose Reductase activity among diabetic patients. Erythrocyte Aldose Reductase activity and fasting plasma glucose levels significantly correlated with the erythrocyte sorbitol level in all individuals (r = 0.48, P less than 0.005 and r = 0.63, P less than 0.005, respectively). The sorbitol level was higher in patients with high Aldose Reductase activity than in those who had low Enzyme activity for any given level of glycemia. The sorbitol production rate calculated from Km and Vmax values showed a better correlation with the erythrocyte sorbitol level (r = 0.80, P less than 0.005), and there was also a good correlation between the erythrocyte sorbitol level and the product of Aldose Reductase activity by plasma glucose level (r = 0.70, P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)