title: Regulation of urea synthesis by glucose and glucagon in normal man.
abstract: The separate effects of glucose and glucagon on alanine stimulated hepatic amino-N to urea-N conversion, quantified by the Functional Hepatic Nitrogen Clearance (FHNC) (i.e. the linear slope of the relation between urea synthesis rate and blood alpha-amino-N concentration), were studied in 7 healthy subjects. FHNC was measured four times in each: during constant infusion of alanine alone; alanine superimposed on constant glucose infusion; alanine superimposed on glucose and low stepwise glucagon infusions; and alanine super-imposed on glucose and high constant glucagon infusions. Glucose halved the glucagon response to alanine. This reduction was abolished by the low stepwise glucagon infusion, aimed at re-establishing portal glucagon levels. The high glucagon infusion resulted in 3-fold elevated glucagon levels. During alanine infusion alone FHNC was (mean +/- SEM) 32.5 +/- 1.9 l/h. Glucose reduced FHNC by 43% to 18.4 +/- 0.9 l/h (p < 0.01). The low stepwise glucagon infusion only partially normalized FHNC as reduced by glucose (to 24.6 +/- 1.5 l/h, (p < 0.01 vs alanine alone)). The high glucagon infusion increased FHNC by 35% despite hyperglycaemia (to 44.1 +/- 1.5 l/h, (p < 0.01 vs alanine alone)). The results show that both glucose and glucagon are independent but opposite regulators of hepatic amino-N conversion. The physiological glucose effect is accomplished by a combination of both the effect of glucose itself and the inhibition by glucose of the glucagon response to alanine. Hyperglucagonaemia increases FHNC and overrules the inhibition by glucose. This may explain the defect nitrogen sparing by glucose and to some extent the catabolism in hyperglucagonaemic stress conditions, despite prevailing hyperglycaemia.
authors.affiliation: Department of Medicine A-2151, Division of Hepatology Rigshospitalet, Copenhagen, Denmark.
authors.forename: O
authors.initials: O
authors.lastname: Hamberg
authors.forename: H
authors.initials: H
authors.lastname: Vilstrup