Increased capacity of urea synthesis in streptozotocin diabetes in rats

Abstract

Diabetes was induced in Wistar rats by intravenous streptozotocin, 75 mg/kg. Four and 14 days after streptozotocin, fasting insulin decreased to about one-third, and fasting glucagon increased three-fold. The urea-N synthesis rate, stimulated by infusion of alanine, was measured at different amino acid concentrations 14 days after streptozotocin in 24 rats. The relationship was compatible with a barrier limited substrate inhibition kinetics. Data were examined accordingly by non-linear regression analysis. Among the estimated kinetic constants, only the 70% increase in Vmax was different from control values. In control rats the capacity of urea nitrogen synthesis, as measured within the amino acid concentration interval 7.3-11.6 mmol/l, was 10.2 +/- 1.1 mumol . (min 100 g BW)-1 (mean +/- SEM). The capacity was not different in 4 day diabetic rats, whereas it doubled in 14 day diabetic rats, 20.9 +/- 1.7 mumol (min 100 g BW)-1. The alanine elimination rate was 35% higher in the 14 day diabetic rats compared both to 4 day diabetic and control rats. The increase of urea synthesis is suggested to be due to enzyme induction by glucagon. The net nitrogen balance was negative at amino acid concentrations up to 25 mmol/l, indicating that the urea synthesis was increased at the expense of amino nitrogen.