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

Jørgen Jensen, Puntip Tantiwong, Jorid T. Stuenæs, Marjorie Molina-Carrion, Ralph A. de Fronzo, Kei Sakamoto, Nicolas Musi

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9 Scopus citations

Abstract

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 V̇O 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 ≈0.5 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 (US)
Pages (from-to)E82-E89
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume303
Issue number1
DOIs
StatePublished - Jul 1 2012

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Keywords

  • Insulin resistance

ASJC Scopus subject areas

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

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