Wortmannin inhibits both insulin- and contraction-stimulated glucose uptake and transport in rat skeletal muscle

Jørgen Wojtaszewski, B F Hansen, Birgitte Ursø, Erik A. Richter

    Research output: Contribution to journalJournal articleResearchpeer-review

    87 Citations (Scopus)

    Abstract

    The role of phosphatidylinositol (PI) 3-kinase for insulin- and contraction-stimulated muscle glucose transport was investigated in rat skeletal muscle perfused with a cell-free perfusate. The insulin receptor substrate-1-associated PI 3-kinase activity was increased sixfold upon insulin stimulation but was unaffected by contractions. In addition, the insulin-stimulated PI 3-kinase activity and muscle glucose uptake and transport in individual muscles were dose-dependently inhibited by wortmannin with one-half maximal inhibition values of approximately 10 nM and total inhibition at 1 microM. This concentration of wortmannin also decreased the contraction-stimulated glucose transport and uptake by approximately 30-70% without confounding effects on contractility or on muscle ATP and phosphocreatine concentrations. At higher concentrations (3 and 10 microM), wortmannin completely blocked the contraction-stimulated glucose uptake but also decreased the contractility. In conclusion, inhibition of PI 3-kinase with wortmannin in skeletal muscle coincides with inhibition of insulin-stimulated glucose uptake and transport. Furthermore, in contrast to recent findings in incubated muscle, wortmannin also inhibited contraction-stimulated glucose uptake and transport. The inhibitory effect of wortmannin on contraction-stimulated glucose uptake may be independent of PI 3-kinase activity or due to inhibition of a subfraction of PI 3-kinase with low sensitivity to wortmannin.

    Original languageEnglish
    JournalJournal of Applied Physiology
    Volume81
    Issue number4
    Pages (from-to)1501-1509
    Number of pages9
    ISSN8750-7587
    Publication statusPublished - 1996

    Keywords

    • 1-Phosphatidylinositol 4-Kinase
    • Adenosine Triphosphate
    • Androstadienes
    • Animals
    • Electric Stimulation
    • Glucose
    • Hindlimb
    • Hypoglycemic Agents
    • Insulin Antagonists
    • Male
    • Membranes
    • Muscle Contraction
    • Muscle, Skeletal
    • Oxygen Consumption
    • Phosphocreatine
    • Phosphorylation
    • Phosphotransferases (Alcohol Group Acceptor)
    • Rats
    • Rats, Wistar
    • Receptor, Insulin

    Cite this