Increased white cell aldose reductase mRNA levels in diabetic patients

Abstract

This paper examines the question of whether diabetes in humans is associated with changes in aldose reductase and sorbitol dehydrogenase gene expression. The polyol pathway, which comprises the enzymes aldose reductase and sorbitol dehydrogenase, is recognised to play a central role in the pathogenesis of the diabetic complications. Whilst it is known that experimental diabetes in the rat is associated with increased aldose reductase gene expression, possibly as an osmoregulatory response to hyperglycaemia, little is known about aldose reductase and sorbitol dehydrogenase gene expression in diabetes in humans. White cell aldose reductase mRNA levels were increased in patients with insulin-dependent (by 135%, P < 0.05) and non-insulin-dependent (by 132%, P < 0.05) diabetes compared to levels in healthy volunteers. Levels of glycosylated haemoglobin were also increased ( P < 0.001) in diabetes but there was no correlation between white cell aldose reductase mRNA and glycosylated haemoglobin levels. In contrast to aldose reductase, levels of white cell sorbitol dehydrogenase mRNA were not affected by diabetes. These results establish for the first time that diabetic patients show increases in white cell aldose reductase mRNA levels, possibly consistent with increased aldose reductase gene expression. This finding may have implications for the use of aldose reductase inhibitors in the treatment of the diabetic complications.