INFLUENCE OF INTERINDIVIDUAL VARIABILITY OF ALDOSE REDUCTASE PROTEIN-CONTENT ON POLYOL-PATHWAY METABOLITES AND REDOX STATE IN ERYTHROCYTES IN DIABETIC-PATIENTS

OBJECTIVE - To clarify the influence of interindividual difference in the level of aldose reductase on the polyol pathway-related metabolism in diabetic patients. RESEARCH DESIGN AND METHODS - The enzyme protei n content was determined by a two-site enzyme-linked immunosorbent ass ay using monoclonal and polyclonal antibodies to recombinant human ald ose reductase in erythrocytes from 35 diabetic patients and 11 healthy volunteers. Patients were stratified into two groups by the median of aldose reductase content, and the erythrocyte sorbitol level, the fru ctose level, and the lactate-to-pyruvate ratio were compared between t he two groups. We also examined the correlation of the enzyme content with these metabolic parameters. RESULTS - The group of patients whose enzyme content was above the median showed a significant increase in the levels of sorbitol (34.7 +/- 4.9 vs. 20.4 +/- 2.0 nmol/g Hb, P < 0 .05) and fructose (99.8 +/- 17.2 vs. 45.9 +/- 4.6 nmol/g Hb, P < 0.05) , along with an elevated lactate-to-pyruvate ratio (28.6 +/- 6.1 vs. 1 1.7 +/- 1.2, P < 0.05), compared with patients with low enzyme levels. The aldose reductase content in erythrocytes was well correlated with its activity, and there was a significant correlation between the enz yme content and the erythrocyte sorbitol (r = 0.58, P < 0.001) or fruc tose (r = 0.57, P < 0.001) levels as well as between the enzyme level and the lactate-to-pyruvate ratio (r = 0.38, P < 0.05). CONCLUSIONS - These results suggest that the interindividual variability of aldose r eductase content may contribute tangibly to the polyol-pathway flux an d cytoplasmic redox alteration in diabetic patients.