Effect of subcutaneous Escherichia coli-induced hypermetabolic sepsis on hepatic gluconeogenesis and its hormonal responsiveness in the rat

I. V. Deaciuc, C. H. Lang, G. J. Bagby, J. J. Spitzer

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Abstract

In hypermetabolic sepsis, gluconeogenesis is markedly elevated during fasting, and is manifested as an increased rate of glucose appearance (R(a)). The likely causes of such a change are alterations in 1) concentration of systemic hormones, 2) concentration of glucose precursors, especially lactate, 3) activity of the key enzymes of the pathway, and 4) hormone receptors and/or transmembrane signalling mechanisms, involved in the hormonal regulation of the pathway. In this study, we investigated the importance of the latter two factors in the increase of gluconeogenesis during hypermetabolic sepsis. Rats were rendered septic by repeated subcutaneous administration of live Escherichia coli. The livers were perfused in vitro in a nonrecirculating mode to measure the rate of gluconeogenesis from saturating concentrations of lactate (5 mM) or lactate (5 mM) + pyruvate (0.5 mM), and the response of gluconeogenesis to vasopressin (VP, 0.1 and 1.0 nM), glucagon (Glc, 0.1 and 1.0 nM), and prostaglandin (PG) F(2α) (5 μM). The rate of gluconeogenesis without precursor supply was ~20-30 μmoles/100 g b w/hr during the first 4-6 min of perfusion, followed by a continuous decline to very low levels. Infusion of lactate (5 mM) or lactate (5 mM) + pyruvate (0.5 mM) increased glucose output, and maintained it at ~100-110 and ~130-140 μmoles/100 g b w/hr, respectively. VP, Glc, and PGF(2α) stimulated the rate of gluconeogenesis in a dose-dependent manner (VP and Glc). No differences were observed between control and septic rats using these stimuli. On the basis of these data, we propose that the increased rate of gluconeogenesis associated with subcutaneous E. coli-induced hypermetabolic sepsis is not due to changes in the maximal capacity of the pathway of gluconeogenesis, or in the response of the liver to gluconeogenic hormones. It seems likely that alterations in the hormonal milieu, associated with an increased substrate availability, play an important role in the augmented gluconeogenesis in hypermetabolic sepsis.

Original languageEnglish (US)
Pages (from-to)82-87
Number of pages6
JournalCirculatory Shock
Volume41
Issue number2
StatePublished - Jan 1 1993

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All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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