Effect of acute exercise on glycogen synthase in muscle from obese and diabetic subjects

Jorgen Jensen, Puntip Tantiwong, Jorid T. Stuenaes, Marjorie Molina-Carrion, Ralph A. DeFronzo, Kei Sakamoto, Nicolas Musi

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    Abstract

    Jensen J, Tantiwong P, Stuenaes JT, Molina-Carrion M, DeFronzo RA, Sakamoto K, Musi N. Effect of acute exercise on glycogen synthase in muscle from obese and diabetic subjects. Am J Physiol Endocrinol Metab 303: E82-E89, 2012. First published April 17, 2012; doi: 10.1152/ajpendo.00658.2011.-Insulin stimulates glycogen synthase (GS) through dephosphorylation of serine residues, and this effect is impaired in skeletal muscle from insulin-resistant [obese and type 2 diabetic (T2DM)] subjects. Exercise also increases GS activity, yet it is not known whether the ability of exercise to affect GS is impaired in insulin-resistant subjects. The objective of this study was to examine the effect of acute exercise on GS phosphorylation and enzyme kinetic properties in muscle from insulin-resistant individuals. Lean normal glucose-tolerant (NGT), obese NGT, and obese T2DM subjects performed 40 min of moderate-intensity cycle exercise (70% of Vo(2max)). GS kinetic properties and phosphorylation were measured in vastus lateralis muscle before exercise, immediately after exercise, and 3.5 h postexercise. In lean subjects, GS fractional activity increased twofold after 40 min of exercise, and it remained elevated after the 3.5-h rest period. Importantly, exercise also decreased GS K-m for UDP-glucose from approximate to 0.5 to approximate to 0.2 mM. In lean subjects, exercise caused significant dephosphorylation of GS by 50-70% (Ser(641), Ser(645), and Ser(645,649,653,657)), and phosphorylation of these sites remained decreased after 3.5 h; Ser(7) phosphorylation was not regulated by exercise. In obese NGT and T2DM subjects, exercise increased GS fractional activity, decreased K-m for UDP-glucose, and decreased GS phosphorylation as effectively as in lean NGT subjects. We conclude that the molecular regulatory process by which exercise promotes glycogen synthesis in muscle is preserved in insulin-resistant subjects.

    Original languageEnglish
    Pages (from-to)E82-E89
    Number of pages8
    JournalAmerican Journal of Physiology, Endocrinology and Metabolism
    Volume303
    Issue number1
    DOIs
    Publication statusPublished - Jul 2012

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