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.

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 ¹⁴CO₂ 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 ¹⁴CO₂ yields for the change in specific activity of glucose 6-phosphate yielded values consistent with the enzyme profile. Calculations from specific yields of ¹⁴CO₂ 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.     

Metabolism via the pentose phosphate pathway in rat pheochromocytoma PC12 cells: Effects of nerve growth factor and 6-aminonicotinamide

Exposure of rat pheochromocytoma PC12 cells to 0.1 mM 6-aminonicotinamide (6AN) for 24 hours resulted in a 500-fold increase in 6-phosphogluconate indicating active metabolism of glucose via the oxidative enzymes of the pentose phosphate pathway. Amounts of 6-phosphogluconate that accumulated in 6AN-treated cells at 24 hours were significantly increased by treatment of the cells with nerve growth factor (NGF) (100 ng 7S/ml) suggesting that metabolism of glucose via the pentose pathway at this time was enhanced by NGF. This stimulation of metabolism via the pentose pathway is probably a late response to NGF because initial rates of 6-phosphogluconate accumulation in 6AN-treated cells were the same in the presence and absence of NGF. Moreover, amounts of¹⁴CO₂ generated from 1-[¹⁴CO₂]glucose during the initial six hour incubation period were the same in control and NGF-treated cells. Specific activities of hexose phosphates labeled from 1-[¹⁴CO₂]glucose were also the same in control and NGF-treated cells. The observation that 6AN inhibited metabolism via the pentose phosphate pathway but failed to inhibit NGF-stimulated neurite outgrowth suggests that NADPH required for lipid biosynthesis accompanying NGF-stimulated neurite outgrowth from PC12 cells can be derived from sources other than, or in addition to, the oxidative enzymes of the pentose phosphate pathway.Special Issue dedicated to Dr. O. H. Lowry.