AJP - Renal Physiology, Vol 242, Issue 5 491-F498, Copyright © 1982 by American Physiological Society
Nonoxidative glucose metabolism a prerequisite for formation of dilute urine
A. D. Baines and B. D. Ross
To examine links between norepinephrine- (NE) stimulated sodium transport
and gluconeogenesis, we perfused isolated rat kidneys with 6% albumin,
containing various combinations of glucose, alanine, pyruvate. and lactate
and inhibitors of gluconeogenesis (0.1 mM mercaptopicolinate, MP) or
glucose metabolism (0.2-0.5 mM 2-deoxyglucose, DG). Inulin clearance,
fractional potassium reabsorption, total sodium reabsorption, and free
water clearance were higher in kidneys perfused with 5 mM glucose plus 2 mM
alanine than in kidneys perfused with either 10 mM lactate or 5 mM
pyruvate. NE, added after 40 min of perfusion, decreased fractional sodium
and potassium excretion in all experiments. In lactate- and/or
pyruvate-perfused kidneys NE decreased fractional water excretion with
little increase in free water clearance; free water formation was lowest in
kidneys perfused with DG or MP. Glucose (5 mM) reversed the inhibitory
effect of MP on free water clearance. In glucose-perfused kidneys NE did
not decrease fractional water excretion, whereas free water clearance
increased threefold. NE stimulated glucose production from pyruvate
2.4-fold and from lactate 1.6-fold. MP inhibited gluconeogenesis both in
the basal state and after NE. We conclude that the formation of dilute
urine requires nonoxidative glucose metabolism to maintain low water
permeability in the diluting segment and a high peritubular glucose
concentration that is ensured by gluconeogenesis in adjacent proximal
tubules.
