Exercise regulates Akt and glycogen synthase kinase-3 activities in human skeletal muscle.
Activation of Akt and deactivation of GSK3 are critical signals regulating a number of cellular processes in multiple systems. Whether physical exercise alters Akt and GSK3 activity in human skeletal muscle is controversial. beta-Catenin, a GSK3 substrate and important Wnt signaling protein that alters gene transcription, has not been investigated in human skeletal muscle. In the present study, eight healthy human subjects performed 30min of cycling exercise at 75% of maximum workload (submaximal) followed by 6 bouts of 60s at 125% maximum workload (maximal). Biopsies of vastus lateralis muscle were taken at rest (basal), and within 15s following cessation of the submaximal and maximal exercise bouts. Exercise at both submaximal and maximal intensities significantly increased Akt activity (40% and 110%, respectively). Increases in Akt activity were accompanied by increases in Akt Thr(308) and Ser(473) phosphorylation, decreased GSK3alpha activity ( approximately 30% at both intensities), and increased phosphorylation of GSK3alpha Ser(21). Exercise at both intensities also decreased beta-catenin Ser(33/37)Thr(41) phosphorylation (50-60% at both intensities). These results demonstrate that Akt, GSK3, and beta-catenin signaling are regulated by exercise in human skeletal muscle, and as such identify them as possible molecular mediators of exercise's effect on metabolic and transcriptional processes in skeletal muscle.
Sakamoto
Kei
K
Research Division, Joslin Diabetes Center and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Arnolds
David E W
DE
Ekberg
Ingvar
I
Thorell
Anders
A
Goodyear
Laurie J
LJ
D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D003598:Cytoskeletal Proteins / Q000378:metabolism; D015444:Exercise; D005260:Female; D006003:Glycogen / Q000378:metabolism; D038341:Glycogen Synthase Kinases / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000097:blood; D019344:Lactic Acid / Q000097:blood; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism; D051176:beta Catenin
D001786:Blood Glucose; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D007328:Insulin; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D051176:beta Catenin; D019344:Lactic Acid; D006003:Glycogen; D038341:Glycogen Synthase Kinases; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt