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Originally published In Press as doi:10.1074/jbc.M004812200 on September 29, 2000

J. Biol. Chem., Vol. 276, Issue 2, 952-956, January 12, 2001
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Regulation of Glycogen Synthesis by Amino Acids in Cultured Human Muscle Cells*

Jane L. ArmstrongDagger , Sylvie M. Bonavaud, Barry J. Toole, and Stephen J. Yeaman§

From the School of Biochemistry and Genetics, Medical School, University of Newcastle, Newcastle Upon Tyne NE2 4HH, United Kingdom

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 p70s6k 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 p90rsk.

* This work was supported by the British Diabetic Association.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger Holds a studentship from the Biotechnology and Biological Sciences Research Council, United Kingdom.

§ To whom correspondence should be addressed: School of Biochemistry and Genetics, Medical School, University of Newcastle, Framlington Place, Newcastle Upon Tyne NE2 4HH, UK. Tel: 44-191-222-7433; Fax: 44-191-222-7424; E-mail: s.j.yeaman@ncl.ac.uk.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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