Regulation of hexokinase II activity and expression in human muscle by moderate exercise

Janice A. Koval, Ralph A. DeFronzo, Robert M. O'Doherty, Richard Printz, Hossein Ardehali, Daryl K. Granner, Lawrence J. Mandarino

Research output: Contribution to journalArticlepeer-review

70 Scopus citations


A single bout of exercise increases the rate of insulin-stimulated glucose uptake and metabolism in skeletal muscle. Exercise also increases insulin-stimulated glucose 6-phosphate in skeletal muscle, suggesting that exercise increases hexokinase activity. Within 3 h, exercise increases hexokinase II (HK II) mRNA and activity in skeletal muscle from rats. It is not known, however, if a single bout of moderate-intensity exercise increases HK II expression in humans. The present study was undertaken to answer this question. Six subjects had percutaneous biopsies of the vastus lateralis muscle before and 3 h after a single 3-h session of moderate-intensity aerobic (60% of maximal oxygen consumption) exercise. Glycogen synthase, HK I, and HK II activities as well as HK I and HK II mRNA content were determined from the muscle biopsy specimens. The fractional velocity of glycogen synthase was increased by 446 ± 84% after exercise (P < 0.005). Hexokinase II activity in the soluble fraction of the homogenates increased from 1.2 ± 0.4 to 4.5 ± 1.6 pmol · min-1 · μg-1 (P < 0.05) but was unchanged in the particulate fraction (4.3 ± 1.3 vs. 5.3 ± 1.5). HK I activity in neither the soluble nor particulate fraction changed after exercise. Relative to a 28S rRNA control signal, HK II mRNA increased from 0.091 ± 0.02 to 0.195 ± 0.037 (P < 0.05), whereas HK I mRNA was unchanged (0.414 ± 0.061 vs. 0.498 ± 0.134, P < 0.20). The increase in HK II activity after moderate exercise in healthy subjects could be one factor responsible for the enhanced rate of insulin-stimulated glucose uptake seen after exercise.

Original languageEnglish (US)
Pages (from-to)E304-E308
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number2 37-2
StatePublished - Feb 1998
Externally publishedYes


  • Exercise
  • Glucose uptake
  • Hexokinase
  • Skeletal muscle

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)


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