The Effect of Acute Uraemia on Gluconeogenesis in Isolated Perfused Rat Livers

Abstract

Abetraet. The effect of acute uraemia on glucose and urea formation by isolated perfused liven of fasting rats was investigated.The basal gluconeogenesis following nephrectomy was significantly increased as compared to normal and sham operated controls. Enhanced glucose formation was associated with an increase in both urea synthesis and output of the p r l y metabolizable amino acids valine, leucine, and isoleucine. In the presence of a mixture of amino acids (serine, threonine, lysine, glutamic acid, ornithine, and citrnlline) all added at near physiological concentrations, the stimulating effect of uraemia on gluconeogenesis was further enhanced. This was paralleled by an increased formation of urea and an increased uptake of the amino acids. It is concluded that acute uraemia may stimulate glucose synthesis by increased substrate supply. This seems to be achieved by a t least two different mechanisms, namely increased protein degradation and accelerated amino acid utilization.

Possible sites of interaction of acute renal failure with amino acid utilization for gluconeogenesis in isolated perfused rat liver

“…Normal, non-operated controls were omitted in the present experiments (perfusions with AIB excepted), as in previous studies no significant differences were found between these animals and sham-operated ones [8]. As has been shown previously in this and other laboratories, these animals quickly develop a severe uraemic syndrome* with an increase in urea and creatinine, the appearance of marked acidosis and a shift of the whole animal's metabolism towards a prevailing catabolic state [8, .…”

“…The sources of chemicals and animals have been described elsewhere [8]. [ 1 -14C ]a-aminoisobutyric acid (AIB) was purchased from New England Nuclear Corp. (Dreieichenhain) and was of more than 99% radiochemical purity.…”

“…Media were analysed as described elsewhere [8,14,151 . Radioactivity of [ 1 -14C] AIB was determined in a Tricarb Scintillation counter (Fa.…”

“…We were led by these findings to investigate carbohydrate metabolism in isolated livers of acute uraemic rats [8]. We demonstrated that in this model uraemia was associated with increased gluconeogenesis, either from endogenous sources or from added amino acids.…”

Metabolism of p-aminobenzoic Acid in the Perfused Livers of Chronically Uraemic Rats

“…More complex adaptations than direct inhibition by substances circulating in uraemic serum must therefore account for these findings. Increased gluconeogenesis has also been reported in the isolated perfused livers of acutely uraemic rats (Frohlich, Scholmerich, Hoppe Seyler, Maier, Talke, Schollmeyer & Gerok, 1974).…”