Regulation of hexokinase II and glycogen synthase mRNA, protein, and activity in human muscle

L. J. Mandarino, R. L. Printz, K. A. Cusi, P. Kinchington, R. M. O'Doherty, H. Osawa, C. Sewell, A. Consoli, D. K. Granner, R. A. DeFronzo

    Research output: Contribution to journalArticlepeer-review

    110 Scopus citations


    Insulin regulates the activity of key enzymes of glucose metabolism in skeletal muscle by altering transcription or translation or by producing activity-altering modifications of preexisting enzyme molecules. Because of the small size of percutaneous muscle biopsies, these phenomena have been difficult to study in humans. This study was performed to determine how physiological hyperinsulinemia regulates the activities of hexokinase (HK), glycogen synthase (GS), and GLUT-4 in human skeletal muscle in vivo. We determined mRNA abundance, protein content, and activities for these proteins in muscle biopsies before and after a hyperinsulinemic clamp in normal subjects. HK I, HK II, GS, and GLUT-4 were expressed in muscle. HK II accounted for 80% of total HK activity and was increased by insulin from a basal value of 2.11 ± 0.26 to 3.35 ± 0.47 pmol · min-1 · mg protein- 1 (P < 0.05); HK I activity was unaffected. Insulin increased GS activity from 3.85 ± 0.82 to 6.06 ± 0.49 nmol · min-1 · mg-1 (P < 0.01). HK II mRNA was increased 3.3 ± 1.3-fold (P < 0.05) by insulin infusion. HK I, GS, and GLUT-4 mRNA and protein were unaffected. Because insulin infusion increased HK II but not GS mRNA, we conclude that HK II and GS may be regulated by insulin by different mechanisms in human skeletal muscle.

    Original languageEnglish (US)
    Pages (from-to)E701-E708
    JournalAmerican Journal of Physiology - Endocrinology and Metabolism
    Issue number4 32-4
    StatePublished - 1995


    • humans
    • insulin
    • skeletal muscle

    ASJC Scopus subject areas

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


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