Effects of hypophysectomy on lactate metabolism in the perfused rat liver

L. S. Jefferson, J. W. Robertson, E. L. Tolman

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Abstract

Various aspects of lactate metabolism were compared in perfused livers from normal and hypophysectomized rats. Glucose production by livers from hypophysectomized animals exceeded that by normal rat livers largely due to enhanced rates of lactate gluconeogenesis. When perfusion was carried out with a noncirculating medium containing physiological levels of lactate (1 to 4 mM), the rate of glucose synthesis from labeled lactate by livers from hypophysectomized rats was 3 to 4 times that of normal rat livers. Saturating levels of substrate were 6 to 8 mM lactate for livers from hypophysectomized rats and 14 mM lactate for normal rat livers. At these levels, the rates of gluconeogenesis in both groups were similar. Over a range of lactate concentrations from physiological to saturating levels, the rates of conversion of lactate to CO2, glycogen, protein, and fatty acids were reduced below normal in livers from hypophysectomized rats. In livers perfused with 1 mM lactate, tissue levels of pyruvate, P enolpyruvate, 2 P glycerate, 3 P glycerate, and glucose 6 P were increased above normal by hypophysectomy. At saturating lactate concentrations, levels of gluconeogenic intermediates in livers from normal and hypophysectomized rats were similar. These data, in addition to the similar rates of total lactate utilization, indicated that hypophysectomy affected a redistribution of substrate among competitive metabolic pathways. It was suggested that at physiological levels of lactate a reduction on pyruvate oxidation led to an increased availability of substrate for gluconeogenesis. The hepatic level of cyclic adenosine 3':5' monophosphate was unchanged following hypophysectomy, suggesting that the increased rate of gluconeogenesis was not due to an elevation in the concentration of the nucleotide. Livers from hypophysectomized rats did not appear to respond to conditions which elevate the tissue level of this nucleotide since an overnight fast, or perfusion with glucagon, had no effect on the rate of conversion of lactate to glucose.

Original languageEnglish (US)
Pages (from-to)4561-4567
Number of pages7
JournalJournal of Biological Chemistry
Volume248
Issue number13
StatePublished - Dec 1 1973

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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