Time Dependent Stimulating Effect of Glucagon on the Capacity of Urea-N Synthesis in Rats

Summary

The effect of glucagon on the capacity of urea-N synthesis was examined in 24 rats as a function of time. First, the conditions for saturation of urea synthesis under glucagon influence were studied by the kinetics of urea-N synthesis rate in relation to arterial blood alpha-amino-N concentration between 5 and 17 mmol/l in 21 nephrectomized rats given zincglucagon (20 μg s.c. per day) for 14 days. Alanine was infused so that steady state concentrations of total alpha-amino-N was attained in each rat. The urea-N synthesis rate was calculated as accumulation in total body water corrected for intestinal hydrolysis.

The relationship suggested a barrier limited substrate inhibition kinetics, as earlier found in control rats, and data were examined accordingly by non-linear regression analysis. The estimated kinetic constants were: V_max = 71 μmol/(min · 100 g body wt), K_m = 5.4 mmol/l, K_i = 2.4mmol/l, and the barrier = 4.4 mmol/l. V_max was increased three times compared with controls. The capacity of urea-N synthesis, i.e. the zenith of the relation, was attained in the concentration interval 7.5 to 12.0 mmol/l, as in controls. The capacity of urea-N synthesis was determined during i.v. infusion of zincglucagon (0.15 μg per min) and after 2, 8, and 14 days of daily s.c. injections of 20 μg zincglucagon. Rats given zincprotamine solution were controls. In the control animals the capacity of urea-N synthesis was 7.4±2.2μmol/(min · 100g body wt), (mean ± SD) during i.v. glucagon 8.1 ± 1.2 μmol/(min · 100g body wt) and after 2, 8, and 14 days of zincglucagon 12.7 ±4.6, 13.4±3.1, and 20.4 ± 2.5 μmol/(min · 100g body wt), respectively.

Thus there was no acute effect of glucagon on the capacity of urea-N synthesis, whereas there was a marked time dependent increase after zincglucagon treatment. The results suggest that regulation of urea kinetics by glucagon may be of importance for the protein wasting frequently encountered during chronic disease states with hyperglucagonemia such as diabetes or uremia.

Key-Words

Metabolism - Nitrogen Conversion - Hormones