Regulation of glycogen synthesis by amino acids in cultured human muscle cells.
Insulin and a number of metabolic factors stimulate glycogen synthesis and the enzyme glycogen synthase. Using human muscle cells we find that glycogen synthesis is stimulated by treatment of the cells with lithium ions, which inhibit glycogen synthase kinase 3. Insulin further stimulates glycogen synthesis in the presence of lithium ions, an effect abolished by wortmannin and rapamycin. We report also that amino acids stimulate glycogen synthesis and glycogen synthase, these effects also being blocked by rapamycin and wortmannin. Amino acids stimulate p70(s6k) and transiently inhibit glycogen synthase kinase 3 without effects on the activity of protein kinase B or the mitogen-activated protein kinase pathway. Thus, the work reported here demonstrates that amino acid availability can regulate glycogen synthesis. Furthermore, it demonstrates that glycogen synthase kinase 3 can be inactivated within cells independent of activation of protein kinase B and p90(rsk).
Armstrong
J L
JL
School of Biochemistry and Genetics, Medical School, University of Newcastle, Newcastle Upon Tyne NE2 4HH, United Kingdom.
Bonavaud
S M
SM
Toole
B J
BJ
Yeaman
S J
SJ
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000494:pharmacology*; D000730:Androstadienes / Q000494:pharmacology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000096:biosynthesis*; D038362:Glycogen Synthase Kinase 3; D038341:Glycogen Synthase Kinases; D006801:Humans; D007700:Kinetics; D008094:Lithium / Q000494:pharmacology; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009842:Oligopeptides / Q000737:chemistry / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D019893:Ribosomal Protein S6 Kinases / Q000037:antagonists & inhibitors; D020123:Sirolimus / Q000494:pharmacology; D000077191:Wortmannin
D000596:Amino Acids; D000730:Androstadienes; D009842:Oligopeptides; D011518:Proto-Oncogene Proteins; D006003:Glycogen; D008094:Lithium; D038341:Glycogen Synthase Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D019893:Ribosomal Protein S6 Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D038362:Glycogen Synthase Kinase 3; D005947:Glucose; D020123:Sirolimus; D000077191:Wortmannin