Exogenous hyperglucagonaemia in insulin controlled diabetic rats increases urea excretion and nitrogen loss from organs

Abstract

In order to study the effect of hyperglucagonaemia on nitrogen metabolism in diabetes, zinc protamin glucagon 60 μg was injected subcutaneously 3 times daily for 4 weeks into streptozotocindiabetic rats (n=5), adequately treated with long acting insulin. This raised the plasma concentration of glucagon to 725±125 (mean±SEM), which is not different from that found in portal blood of uncontrolled diabetic rats: 400±75 ng/l. The controls were 5 diabetic rats treated with insulin alone and 5 non-diabetic rats. Compared with control rats the nitrogen balance was reduced (p<0.05) and the nitrogen contents of carcass, heart, intestines, and kidneys were reduced by 15-30% (p<0.05) in the glucagon treated rats. The hepatic capacity of urea synthesis and the alanine elimination rate were determined in the 3 above-mentioned groups, and confirmed in 3 identical groups followed for only 2 weeks; and in addition in a group of glucagon treated diabetic rats, where the long acting glucagon was substituted by neutral insulin the last two days before investigation. The capacity of urea-N synthesis and the alanine elimination rate were, respectively, in control rats: 9.6±0.8 and 5.9±0.3 μmol/(min 100 g body weight), in insulin treated diabetic rats: 8.5±0.7 and 5.4±0.6 μmol/(min 100g body weight), in glucagon treated rats: 6.3±0.4 (lower than controls, p<0.05) and 10.4±0.4 (higher than controls, p<0.05) (μmol/(min 100 g body weight), and in glucagon treated rats given neutral insulin: 20.7±1.6 and 10.9±0.3 μmol/(min 100 g body weight) (both higher than controls, p<0.05). Hyperglucagonaemia in itself leads to loss of nitrogen from organs, probably by an increased hepatic conversion of amino-nitrogen to urea-nitrogen, as evidenced by the increased urea excretion. This proceeds despite an insulin induced decrease in the capacity of urea synthesis and may thus rather be attributed to changes in the affinity of urea synthesis for amino-nitrogen. © 1988 Springer-Verlag.