, Volume 37, Supplement 2, pp S155–S161 | Cite as

Mechanisms modifying glucose oxidation in diabetes mellitus

  • P. J. Randle
  • D. A. Priestman
  • S. Mistry
  • A. Halsall


The Glucose Fatty Acid Cycle as formulated 30 years ago and reviewed in the Minkowski lecture in 1966 described short term effects of fatty acids (minutes) to decrease uptake, glycolysis and oxidation of glucose in heart and skeletal muscles. Such short term effects have since been extended to include inhibition of glucose uptake and glycolysis and stimulation of gluconeogenesis in liver and these effects have also been convincingly demonstrated in man in vivo. More recently a longer term effect of fatty acid metabolism to decrease glucose oxidation (hours) has been shown in heart and skeletal muscle and liver. This effect increases the specific activity of pyruvate dehydrogenase kinase, which in turn results in enhanced phosphorylation and inactivation of the pyruvate dehydrogenase complex. Activity of the pyruvate dehydrogenase complex is the major determinant of glucose oxidation rate. It seems likely that longer term effects of fatty acids on this and other aspects of glucose metabolism could be important in the development of insulin resistance in diabetes mellitus in man.

Key words

Glucose fatty acid cycle glucose oxidation diabetes mellitus starvation pyruvate dehydrogenase complex pyruvate dehydrogenase kinase pyruvate dehydrogenase phosphatase fatty acids cyclic AMP cultured hepatocytes cultured cardiac myocytes soleus muscle insulin action insulin resistance 



Pyruvate dehydrogenase


kinase activator protein


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Copyright information

© Springer-Verlag 1994

Authors and Affiliations

  • P. J. Randle
    • 1
  • D. A. Priestman
    • 1
  • S. Mistry
    • 1
  • A. Halsall
    • 1
  1. 1.Nuffield Department of Clinical BiochemistryUniversity of Oxford, John Radcliffe HospitalOxfordUK

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