Authors: S Ii M Ohta E Kudo T Yamaoka T Tachikawa M Moritani M Itakura K Yoshimoto
Publish Date: 2004/03/01
Volume: 47, Issue: 3, Pages: 541-548
Abstract
We created mice hARTgSDH null with transgenederived human aldose reductase and sorbitol dehydrogenase SDH deficiency and analysed i the contribution of accumulated sorbitol to urinary albumin excretion rate and ii the effect of the aldose reductase inhibitor epalrestat on the diabetic redox state including decreased renal reduced glutathione concentrations or increased lactate to pyruvate ratios in the diabetic kidneyCompared to littermates nondiabetic transgenic mice had a 26fold increase in aldose reductase mRNA In a diabetic group aldose reductase mRNA in hARTg mice was 27fold higher than in littermates In the diabetic and nondiabetic groups hARTgSDH null mice had the highest sorbitol content among all four genetic types including hARTgSDH null SDH null hARTg and littermates The urinary albumin excretion rate in nondiabetic groups was similar in the four genetic types of mouse In diabetic groups it was greater than in nondiabetic groups but did not correlate with the sorbitol content among the four genetic types of mouse When aldose reductase inhibitor and streptozotocin were given simultaneously at 6 weeks of age epalrestat prevented diabetic increases in urinary albumin excretion rate and completely prevented diabetic decreases in reduced glutathione concentrations and diabetic increases in lactate to pyruvate ratios even in the presence of transgenic aldose reductase
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