Regulation of pathways of glucose metabolism in kidney. The effect of experimental diabetes on the activity of the pentose phosphate pathway and the glucuronate-xylulose pathway

Abstract

Measurements have been made of the activities of enzymes of the pentose phosphate pathway, the glucuronate-xylulose pathway, hexokinase and phosphofructokinase in kidney of diabetic and normal rats. The activities of these enzymes keep pace with kidney growth, remaining constant per gram tissue but showing a marked increase on the basis of total activity per 100 g body wt. The formation of 14CO 2 from [1- 14C]glucose and [6- 14C]glucose by kidney slices from diabetic rats was decreased to approximately half the control value; evidence was obtained for an equivalent dilution of the glucose 6-phosphate pool. Correction of the 14CO 2 yields for the change in specific activity of glucose 6-phosphate yielded values consistent with the enzyme profile. Calculations from specific yields of 14CO 2 provided evidence for an increased flux of glucose via the pentose phosphate pathway in the kidney in diabetes. The results are discussed in relation to kidney hypertrophy in diabetes and the requirement for ribose 5-phosphate and NADPH for biosynthetic reactions and in relation to the thickening of the basement membrane in diabetes. These results are in accord with the concept of glucose overutilization by non-insulin-requiring tissues.