The Role of Glucose in the Regulation of Substrate Interaction during Exercise

Labros S. Sidossis

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Glucose and fatty acids are the main energy sources for oxidative metabolism in endurance exercise. Although a reciprocal relationship exists between glucose and fatty acid contribution to energy production for a given metabolic rate, the controlling mechanism remains debatable. Randle et al.'s (1963) glucose-fatty acid cycle hypothesis provides a potential mechanism for regulating substrate interaction during exercise. The cornerstone of this hypothesis is that the rate of lipolysis, and therefore fatty acid availability, controls how glucose and fatty acids contribute to energy production. Increasing fatty acid availability attenuates carbohydrate oxidation during exercise, mainly via sparing intramuscular glycogen. However, there is little evidence for a direct inhibitory effect of fatty acids on glucose oxidation. We found that glucose directly determines the rate of fat oxidation by controlling fatty acid transport into the mitochondria. We propose that the intracellular availability of glucose, rather than fatty acids, regulates substrate interaction during exercise.

Original languageEnglish (US)
Pages (from-to)558-569
Number of pages12
JournalCanadian Journal of Applied Physiology
Issue number6
StatePublished - Dec 1998


  • Carnitine palmitoyltransferase
  • Free fatty acids
  • Malonyl-coenzyme A
  • Medium-chain fatty acids
  • Mitochondria

ASJC Scopus subject areas

  • Physiology
  • Orthopedics and Sports Medicine


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