Inhibition of hepatic gluconeogenesis by dichloroacetate

Research output: Contribution to journalArticle

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Abstract

Gluconeogenesis from lactate by isolated hepatocytes suspended in a low bicarbonate medium is effectively inhibited by the hypoglycemic agent dichloroacetate. With this medium dichloroacetate suppresses the accumulation of the components of the malateaspartate shuttle, limits mitochondrial utilization of cytoplasmic reducing equivalents, and makes the availability of pyruvate and/or oxaloacetate limiting for gluconeogenesis. Much less inhibition is observed with hepatocytes suspended in a medium (Krebs-Henseleit saline) containing physiological concentrations of bicarbonate. No inhibition is observed with Krebs-Henseleit saline supplemented with lysine as a source of amino groups for the malate-aspartate shuttle. Thus, dichloroacetate inhibition of gluconeogenesis is observed only when hepatocytes are incubated in a medium deficient in bicarbonate and amino acids. This means that the action of dichloroacetate as a hypoglycemi agent is best explained by stimulation of peripheral tissue utilization of glucose and potential precursors for hepati gluconeogenesis rather than by direct inhibition of hepatic gluconeogenesis.

Original languageEnglish
Pages (from-to)364-371
Number of pages8
JournalArchives of Biochemistry and Biophysics
Volume189
Issue number2
DOIs
StatePublished - 1978

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Gluconeogenesis
Bicarbonates
Liver
Hepatocytes
Oxaloacetic Acid
Pyruvic Acid
Hypoglycemic Agents
Aspartic Acid
Lysine
Lactic Acid
Availability
Tissue
Amino Acids
Glucose

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Inhibition of hepatic gluconeogenesis by dichloroacetate. / Harris, Robert; Crabb, David.

In: Archives of Biochemistry and Biophysics, Vol. 189, No. 2, 1978, p. 364-371.

Research output: Contribution to journalArticle

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