GLUT4 and glycogen synthase are key players in bed rest-induced insulin resistance
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GLUT4 and glycogen synthase are key players in bed rest-induced insulin resistance. / Biensø, Rasmus Sjørup; Jørgensen, Stine Ringholm; Kiilerich, Kristian; Aachmann-Andersen, Niels Jacob; Krogh-Madsen, Rikke; Guerra, Borja; Plomgaard, Peter Stendahl; van Hall, Gerrit; Treebak, Jonas Thue; Saltin, Bengt; Lundby, Carsten; Calbet, Jose A.L.; Pilegaard, Henriette; Wojtaszewski, Jørgen.
In: Diabetes, Vol. 61, No. 5, 2012, p. 1090-1099.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - GLUT4 and glycogen synthase are key players in bed rest-induced insulin resistance
AU - Biensø, Rasmus Sjørup
AU - Jørgensen, Stine Ringholm
AU - Kiilerich, Kristian
AU - Aachmann-Andersen, Niels Jacob
AU - Krogh-Madsen, Rikke
AU - Guerra, Borja
AU - Plomgaard, Peter Stendahl
AU - van Hall, Gerrit
AU - Treebak, Jonas Thue
AU - Saltin, Bengt
AU - Lundby, Carsten
AU - Calbet, Jose A.L.
AU - Pilegaard, Henriette
AU - Wojtaszewski, Jørgen
N1 - CURIS 2012 5200 074
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
KW - Bed Rest
KW - Benzodiazepinones
KW - Blood Glucose
KW - GTPase-Activating Proteins
KW - Gene Expression Regulation
KW - Glucose
KW - Glucose Transporter Type 4
KW - Glycogen
KW - Glycogen Synthase
KW - Humans
KW - Insulin
KW - Insulin Resistance
KW - Male
KW - Muscle, Skeletal
KW - Palmitates
KW - Phosphorylation
KW - Proto-Oncogene Proteins c-akt
U2 - 10.2337/db11-0884
DO - 10.2337/db11-0884
M3 - Journal article
C2 - 22403297
VL - 61
SP - 1090
EP - 1099
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 5
ER -
ID: 40317019