Regulation of urea production by glucose infusion in vivo

We have investigated the acute in vivo regulation of urea production in normal postabsorptive volunteers by administering a primed constant infusion of 15N2-urea to measure urea production during the constant intravenous infusion of equivalent molar quantities of exogenous nitrogen, given as alanine or glutamine, either with or without a simultaneous infusion of glucose at 4 mg.kg-.min-1. These responses were compared with the response to the infusion of glucose alone. Both amino acid infusions elicited significant (P less than 0.05) and identical (26%) increases in urea production over 4 h. When the glucose infusion was added to the amino acid infusions, urea production remained constant, despite the comparable increases in plasma total nonessential amino nitrogen, as were observed with the amino acid infusions alone. Glucose infused alone elicited a significant (P less than 0.05) reduction (18%) in urea production but no corresponding change in plasma total amino nitrogen. We conclude that 1) infused glucose or its hormonal response suppresses urea production by blunting the normal hepatic ureagenic response to a fixed nitrogen load, 2) this suppressive effect is not mediated via a reduction in substrate (nitrogen) supply, and 3) the inhibition of hepatic gluconeogenesis from amino acids represents one component of this suppressive effect, and direct suppression of urea cycle activity probably represents another component.