GLUT4 and Glycogen Synthase Are Key Players in Bed Rest–Induced Insulin Resistance

  1. Jørgen F.P. Wojtaszewski1,7
  1. 1Copenhagen Muscle Research Centre, University of Copenhagen, Copenhagen, Denmark
  2. 2Centre of Inflammation and Metabolism, University of Copenhagen, Copenhagen, Denmark
  3. 3Department of Biology, University of Copenhagen, Copenhagen, Denmark
  4. 4Rigshospitalet, Section 7652, Copenhagen, Denmark
  5. 5Rigshospitalet, Section 7641, Copenhagen, Denmark
  6. 6Department of Physical Education, University of Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain
  7. 7Molecular Physiology Group, Department of Exercise and Sport Sciences, University of Copenhagen, Copenhagen, Denmark
  1. Corresponding author: Rasmus S. Biensø, rsbiensoe{at}


To elucidate the molecular mechanisms behind physical inactivity–induced insulin resistance in skeletal muscle, 12 young, healthy male subjects completed 7 days of bed rest with vastus lateralis muscle biopsies obtained before and after. In six of the subjects, muscle biopsies were taken from both legs before and after a 3-h hyperinsulinemic euglycemic clamp performed 3 h after a 45-min, one-legged exercise. Blood samples were obtained from one femoral artery and both femoral veins before and during the clamp. Glucose infusion rate and leg glucose extraction during the clamp were lower after than before bed rest. This bed rest–induced insulin resistance occurred together with reduced muscle GLUT4, hexokinase II, protein kinase B/Akt1, and Akt2 protein level, and a tendency for reduced 3-hydroxyacyl-CoA dehydrogenase activity. The ability of insulin to phosphorylate Akt and activate glycogen synthase (GS) was reduced with normal GS site 3 but abnormal GS site 2+2a phosphorylation after bed rest. Exercise enhanced insulin-stimulated leg glucose extraction both before and after bed rest, which was accompanied by higher GS activity in the prior-exercised leg than the rested leg. The present findings demonstrate that physical inactivity–induced insulin resistance in muscle is associated with lower content/activity of key proteins in glucose transport/phosphorylation and storage.

  • Received June 27, 2011.
  • Accepted January 16, 2012.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See for details.

| Table of Contents