Nonoxidative glucose metabolism a prerequisite for formation of dilute urine

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Abstract
To examine links between norepinephrine (NE)-stimulated Na transport and gluconeogenesis, isolated rat kidneys were perfused with 6% albumin containing various combinations of glucose, alanine, pyruvate and lactate as well as inhibitors of gluconeogenesis (0.1 mM mercaptopicolinate, MP) or glucose metabolism (0.2-0.5 mM 2-deoxyglucose, DG). Inulin clearance, fractional K reabsorption, total Na reabsorption and free water clearance were higher in kidneys perfused with 5 mM glucose plus 2 mM alanine than in kidneys perfused with 10 mM lactate or 5 mM pyruvate NE, added after 40 min of perfusion, decreased fractional Na and K 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; free water cleareance increased 3-fold. NE stimulated glucose production from pyruvate 2.4-fold and from lactate 1.6-fold. MP inhibited gluconeogenesis in the basal state and after NE. The formation of dilute urine may require 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.