Effects of exercise and insulin on insulin signaling proteins in human skeletal muscle

Janice A. Koval, Katsumi Maezono, Mary Elizabeth Patti, Merri Pendergrass, Ralph A. DeFronzo, Lawrence J. Mandarino

    Research output: Contribution to journalArticle

    37 Scopus citations

    Abstract

    Insulin and exercise independently increase glucose metabolism in muscle. Moreover, exercise training or a prior bout of exercise increases insulin-stimulated glucose uptake in resting skeletal muscle. The present study was undertaken to compare how physiological hyperinsulinemia and moderate intensity aerobic exercise affect the tyrosine phosphorylation state and activity of insulin signaling molecules in healthy, physically inactive volunteers. Subjects had biopsies of the vastus lateralis muscle before and immediately after 30 min of either hyperinsulinemia (euglycemic insulin clamp) or moderate-intensity exercise on a cycle ergometer (~60% of V̇O(2max)). Insulin receptor and IRS-1 tyrosine phosphorylation, association of the p85 regulatory subunit of PI 3-kinase with IRS-1, IRS-1 associated PI 3-kinase activity, and glycogen synthase activity were determined in muscle biopsy specimens taken from healthy subjects before and after insulin or exercise. Physiological hyperinsulinemia increased the rate of glucose disposal from 11.4 ± 1.5 to 25.6 ± 6.7 μmol · kg-1 · min-1 (P < 0.01), insulin receptor and IRS-1 tyrosine phosphorylation (173 ± 19% and 159 ± 35% of basal values, respectively, P < 0.05), association of the p85 regulatory subunit of PI 3-kinase with IRS-1 (159 ± 10%, P < 0.05), and glycogen synthase fractional velocity (136 ± 11%, P < 0.01). Exercise also increased glucose disposal, from 10.4 ± 0.5 to 15.6 ± 1.7 μmol · kg-1 · min-1 (P < 0.01) and glycogen synthase fractional velocity (253 ± 35% of basal, P < 0.01). The exercise-induced increase in glycogen synthase was greater than that due to insulin (P < 0.05). In contrast to insulin, exercise decreased tyrosine phosphorylation of the insulin receptor to 72 ± 10% of basal values (P < 0.05 vs basal and P < 0.05 vs insulin) and had no effect on IRS-1 tyrosine phosphorylation, or association of p85 with IRS-1. The exercise-induced decreased insulin receptor tyrosine phosphorylation could explain the well-known effect of exercise to enhance the sensitivity of muscle to insulin.

    Original languageEnglish (US)
    Pages (from-to)998-1004
    Number of pages7
    JournalMedicine and science in sports and exercise
    Volume31
    Issue number7
    DOIs
    StatePublished - Jul 17 1999

    Keywords

    • Exercise
    • Insulin Receptor
    • Insulin Signaling
    • Skeletal Muscle

    ASJC Scopus subject areas

    • Orthopedics and Sports Medicine
    • Physical Therapy, Sports Therapy and Rehabilitation

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  • Cite this

    Koval, J. A., Maezono, K., Patti, M. E., Pendergrass, M., DeFronzo, R. A., & Mandarino, L. J. (1999). Effects of exercise and insulin on insulin signaling proteins in human skeletal muscle. Medicine and science in sports and exercise, 31(7), 998-1004. https://doi.org/10.1097/00005768-199907000-00012