Nonoxidative glucose metabolism a prerequisite for formation of dilute urine.

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.