GSK-3beta and control of glucose metabolism and insulin action in human skeletal muscle.
The involvement of the beta-isoform of glycogen synthase kinase (GSK-3) in glucose metabolism and insulin action was investigated in cultured human skeletal muscle cells. A 60% reduction in GSK-3beta protein expression was attained by treatment with siRNA; GSK-3alpha expression was unaltered. GSK-3beta knockdown did not influence total glycogen synthase (GS) activity, but increased the phosphorylation-dependent activity (fractional velocity-FV) in the basal state. Insulin responsiveness of GSFV was doubled by GSK-3beta knockdown (p<0.05). Basal rates of glucose uptake (GU) were not significantly influenced by GSK-3beta knockdown, while insulin stimulation of GU was increased. Improvements in insulin action on GS and GU did not involve changes in protein expression of either IRS-1 or Akt 1/2. Maximal insulin stimulation of phosphorylation of Akt was unaltered by GSK-3beta knockdown. Unlike GSK-3alpha, GSK-3beta directly regulates both GS activity in the absence of added insulin and through control of insulin action.
Ciaraldi
T P
TP
Veterans Affairs San Diego Healthcare System and Department of Medicine, University of California, 3350 La Jolla Village Drive, San Diego, CA 92161, USA.
Carter
L
L
Mudaliar
S
S
Henry
R R
RR
D002478:Cells, Cultured; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006006:Glycogen Synthase / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D007328:Insulin; D007527:Isoenzymes; D006006:Glycogen Synthase; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; C448021:glycogen synthase kinase 3 alpha; D005947:Glucose