Hormone effects on hepatic substrate preference in sepsis.
This study addressed the effect of catecholamine stimulation on substrate utilization for gluconeogenesis, ureagenesis, and oxidation in perfused livers from septic rats. Livers were perfused with buffer containing 5 mM [14C]lactate and various concentrations of unlabeled alanine or pyruvate. Addition of alanine to lactate resulted in inhibition of gluconeogenesis and especially inhibition of gluconeogenesis from lactate. This effect was dependent upon the presence of the amino nitrogen, since the effect of pyruvate was to increase total gluconeogenesis with little effect on gluconeogenesis specifically from lactate except with phenylephrine stimulation of livers from sham-operated animals in which addition of pyruvate actually increased the rate of gluconeogenesis from lactate. Alanine itself was very poorly utilized as a gluconeogenic substrate. In contrast, the addition of alanine stimulated total oxygen consumption in both groups in the absence or presence of phenylephrine. This was the result of oxidation of added alanine in livers from sham animals, either with or without phenylephrine, and in septic animals without phenylephrine. However, in the presence of phenylephrine, the increase in total oxygen consumption was almost entirely the result of lactate oxidation. Pyruvate, on the other hand, uniformly stimulated oxygen consumption in both groups, with and without phenylephrine. Urea production was increased by alanine to a greater extent in the septic group compared to sham. However, while phenylephrine stimulated ureagenesis in the sham-operated group, it inhibited ureagenesis in the septic group. These results demonstrate that fundamental differences develop in livers from septic animals in their handling of nitrogenous and non-nitrogenous gluconeogenic substrates.(ABSTRACT TRUNCATED AT 250 WORDS)
Paidas
C N
CN
Division of Pediatric Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, USA.
Clemens
M G
MG
D000409:Alanine / Q000494:pharmacology; D000818:Animals; D004734:Energy Metabolism / Q000187:drug effects*; D005943:Gluconeogenesis / Q000187:drug effects; D006728:Hormones / Q000502:physiology*; D007773:Lactates / Q000494:pharmacology; D019344:Lactic Acid; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D010538:Peritonitis / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology*; D011773:Pyruvates / Q000494:pharmacology; D019289:Pyruvic Acid; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000378:metabolism*; D013379:Substrate Specificity; D014508:Urea / Q000378:metabolism
D006728:Hormones; D007773:Lactates; D011773:Pyruvates; D010656:Phenylephrine; D019344:Lactic Acid; D019289:Pyruvic Acid; D014508:Urea; D000409:Alanine