Isolated hepatocytes from 24-h-starved rats were used to assess the possible effect of Ahe hypoglycaemic agent 3-mercaptopicolinate on flux through the hepatic pyruvate dehydrogenase complex. Increasing the extraceIIular pyruvate concentration from 1 mM to 2 mM or 5 mM resulted in an increase in flux through pyruvate dehydrogenase and the tricarboxylic acid cycle as measured by14CO2 evolution from [1-14C]pyruvate and [3-14C]pyruvate. Gluconeogenesis was inhibited by 3-mercaptopicolinate from both 1 mM and 2 mM pyruvate, but significant increases in malate and citrate concentrations only occurred in cells incubated with 1 mM pyruvate. Flux through pyruvate dehydrogenase was stimulated by 3-mercaptopicolinate with 1 mM pyruvate but was unaltered with 2 mM pyruvate. Dichloroacetate stimulated flux through pyruvate dehydrogenase with no effect on gluconeogenesis in the presence of I mM pyruvate. There was no effect of 3-mercaptopicolinate, administered in vivo, to 24-h-starved rats on the activity of pyruvate dehydrogenase in freeze-clamped heart or liver tissue, although the drug did decrease blood glucose concentration and increase the blood concentrations of lactate and alanine. Dichloroacetate, administered in vivo to 24-h-starved rats, increased the activity of pyruvate dehydrogenase in freeze-clamped heart and liver, and caused decreases in the blood concentrations of glucose, lactate, and alanine. The results suggest that 3-mercaptopicolinate increases flux through hepatocyte pyruvate dehydrogenase by an indirect mechanism.
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May 01 1984
Stimulation of flux through hepatic pyruvate dehydrogenase by 3-mercaptopicolinate
David D. Myles;
David D. Myles
1Department of Biochemistry, Glaxo Group Research, Ware, Hertfordshire, SG12 ODJ, UK
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Peter Strong;
Peter Strong
1Department of Biochemistry, Glaxo Group Research, Ware, Hertfordshire, SG12 ODJ, UK
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Garry D. Stratton;
Garry D. Stratton
1Department of Biochemistry, Glaxo Group Research, Ware, Hertfordshire, SG12 ODJ, UK
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Ian F. Skidmore;
Ian F. Skidmore
1Department of Biochemistry, Glaxo Group Research, Ware, Hertfordshire, SG12 ODJ, UK
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Mary C. Sugden
Mary C. Sugden
2Department of Chemical Pathology, The London Hospital Medical College, Turner Street, London EC1 2AD, UK
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Publisher: Portland Press Ltd
Received:
March 23 1984
Online ISSN: 1573-4935
Print ISSN: 0144-8463
© 1984 The Biochemical Society
1984
Biosci Rep (1984) 4 (5): 441–450.
Article history
Received:
March 23 1984
Citation
David D. Myles, Peter Strong, Garry D. Stratton, Ian F. Skidmore, Mary C. Sugden; Stimulation of flux through hepatic pyruvate dehydrogenase by 3-mercaptopicolinate. Biosci Rep 1 May 1984; 4 (5): 441–450. doi: https://doi.org/10.1007/BF01122510
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