HORMONE EFFECTS ON HEPATIC SUBSTRATE PREFERENCE IN SEPSIS

This study addressed the effect of catecholamine stimulation on substr ate utilization for gluconeogenesis, ureagenesis, and oxidation in per fused livers from septic rats. Livers were perfused with buffer contai ning 5 mM [C-14]lactate and various concentrations of unlabeled alanin e or pyruvate. Addition of alanine to lactate resulted in inhibition o f gluconeogenesis and especially inhibition of gluconeogenesis from la ctate. This effect was dependent upon the presence of the amino nitrog en, since the effect of pyruvate was to increase total gluconeogenesis with little effect on gluconeogenesis specifically from lactate excep t with phenylephrine stimulation of livers from sham-operated animals in which addition of pyruvate actually increased the rate of gluconeog enesis from lactate. Alanine itself was very poorly utilized as a gluc oneogenic substrate. In contrast, the addition of alanine stimulated t otal oxygen consumption in both groups in the absence or presence of p henylephrine. This was the result of oxidation of added alanine in liv ers from sham animals, either with or without phenylephrine, and in se ptic animals without phenylephrine. However, in the presence of phenyl ephrine, the increase in total oxygen consumption was almost entirely the result of lactate oxidation. Pyruvate, on the other hand, uniforml y stimulated oxygen consumption in both groups, with and without pheny lephrine. Urea production was increased by alanine to a greater extent in the septic group compared to sham. However, while phenylephrine st imulated ureagenesis in the sham-operated group, it inhibited ureagene sis in the septic group. These results demonstrate that fundamental di fferences develop in livers from septic animals in their handling of n itrogenous and non-nitrogenous gluconeogenic substrates. These effects appear to be dependent upon the presence of the amino nitrogen group and are highly dependent upon the hormonal milieu.