Folate Metabolism in Streptozotocin-Induced Diabetic Rats

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Metabolic changes in folic acid and their polyglutamyl derivatives were studied in streptozotocin-induced diabetic rats. Polyglutamylfolates, which constituted about 70% of the folates (determined by the Lactobacillus casei microbiological assay) in normal rat liver, were observed to be hydrolyzed to a greater extent to simple monoglutamyl forms as the diabetes progressed. Only 4-5% conjugated folates were observed 25 days after the injection of streptozotocin. Total methylfolates, which represented 70-75% of total folates, were lowered by 60% and methylpolyglutamylfolates by 95% in the diabetic rat. An imbalance in the two folate-metabolizing enzymes, folyl conjugase and folylpolyglutamate synthetase, were observed in diabetes, the former being 2-3-fold higher and the latter being 7-8-fold lower. [¹⁴C]Folate uptake studies indicated that folates accumulated for up to the first 24h in diabetic rat liver, and then were depleted over the next 48h period, indicating an impaired polyglutamylation and storage of folates.