Effect of Diabetes on the Biosynthesis of the Renal Glomerular Basement Membrane: Studies on the Glucosyltransferase

Abstract

Kidney glucosyltransferase (UDP-glucose: galactosylhydroxylysine-basement membrane glucosyltransferase), which is involved in the synthesis of the hydroxylsine-linked disaccharide units of glomerular basement membrane, has been measured in the renal cortices of normal and alloxan diabetic rats. The level of this enzyme in diabetic kidneys was found to be significantly elevated over that of age-matched controls, expressed either as specific or total activity, at all times studied (one to five months). However the difference between the normal and diabetic animalsincreased with the duration of the disease. When short-term diabetics were treated with insulin, the level of the glucosyltransferase could be restored to normal. Insulin treatment of long-term diabetic animals, which were more difficult to control, brought the enzyme level close to normal but did not completely restore it. The glucosyltransferase activity in several other tissues of the alloxan diabetic rat, including lung, liver, testes, spleen, and uterus, did not show any significant elevation over that of the normal. Measurement in kidney of a glycosyltransferase (UDP-galactose :N-acetylglucosamine-glycoprotein galactosyltransferase) involved in the synthesis of a different type of carbohydrate unit did not show the marked elevation noted for the glucosyltransferase. It is believed that the insulin-reversible glucosyltransferase elevation of the diabetic renal cortex reflects the increased basement membrane synthesis occurring in this tissue and indicates that this process is directly or indirectly under the control of this hormone.