INCREASED WHITE CELL ALDOSE REDUCTASE MESSENGER-RNA LEVELS IN DIABETIC-PATIENTS

This paper examines the question of whether diabetes in humans is asso ciated with changes in aldose reductase and sorbitol dehydrogenase gen e expression. The polyol pathway, which comprises the enzymes aldose r eductase and sorbitol dehydrogenase, is recognised to play a central r ole ill the pathogenesis of the diabetic complications Whilst it is kn own that experimental diabetes in the rat is associated with increased aldose reductase gene expression, possibly as an osmoregulatory respo nse ro hyperglycaemia, little is known about aldose reductase and sorb itol dehydrogenase gene expression in diabetes in humans. White cell a ldose reductase mRNA levels were increased in patients with insulin-de pendent (by 135%, P < 0.05) and non insulin-dependent (by 132%, P < 0. 05) diabetes compared to levels in healthy volunteers. Levels of glyco sylated haemoglobin were also increased (P < 0.001) ill diabetes but t here was no correlation between white cell aldose reductase mRNA and g lycosylated haemoglobin levels. In contrast to aldose reductase, level s of white cell sorbitol dehydrogenase mRNA were not affected by diabe tes. These results establish for the first time that diabetic patients show increases in white cell aldose reductase mRNA levels, possibly c onsistent with increased aldose reductase gene expression This finding may have implications for the use of aldose reductase inhibitors in t he treatment of the diabetic complications.