Mechanism for the oleate stimulation of gluconeogenesis from dihydroxyacetone by hepatocytes from fasted rats

Raymond S. Ochs, Robert A. Harris

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Oleate stimulates glucose production and concomitantly decreases lactate and pyruvate production by rat hepatocyte suspensions incubated with dihydroxyacetone as substrate. The actions of oleate could be blocked by d-(+)dodecanoylcarnitine, which inhibits transport of the fatty acid into the mitochondria and the subsequent oxidation. β-Hydroxybutyrate, but not acetoacetate, also stimulated glucose synthesis and inhibited lactate and pyruvate production. Furthermore, both β-hydroxybutyrate and oleate stimulated oxygen consumption to the same extent. This suggests that oleate stimulates glucose production by the provision of energy subsequent to mitochondrial β-oxidation of the fatty acids. The content of ATP itself did not appear to be responsible for the effects of oleate. Crossover analysis of the gluconeogenic intermediates implicated a site of oleate action between fructose 1,6-bisphosphate and fructose 6-phosphate, suggesting phosphofructokinase and/or fructose-bisphosphatase as possible regulatory sites. Coupled with the finding that intracellular citrate accumulates upon addition of oleate or β-hydroxybutyrate, but not acetoacetate, the results suggest that citrate inhibition of phosphofructokinase accounts for the redirection of carbon flow from lactate and pyruvate formation and towards that of glucose.

Original languageEnglish (US)
Pages (from-to)40-47
Number of pages8
JournalBBA - Molecular Cell Research
Volume886
Issue number1
DOIs
StatePublished - Apr 8 1986

Keywords

  • (Rat hepatocyte)
  • Fatty-acid oxidation
  • Gluconeogenesis
  • Glycolysis
  • Phosphofructokinase

ASJC Scopus subject areas

  • Biophysics
  • Cell Biology
  • Molecular Biology

Fingerprint Dive into the research topics of 'Mechanism for the oleate stimulation of gluconeogenesis from dihydroxyacetone by hepatocytes from fasted rats'. Together they form a unique fingerprint.

  • Cite this