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The Molecular Mechanism by Which Insulin Activates Glycogen Synthase in Mammalian Skeletal Muscle

  • Philip Cohen
  • Peter J. Parker
  • James R. Woodgett

Abstract

One of the important metabolic effects of insulin is its ability to stimulate the synthesis of glycogen in skeletal muscle within minutes; much research has been directed toward understanding the molecular basis of this effect. Almost 25 years ago, Joseph Larner and co-workers showed that glycogen synthase, the rate-limiting enzyme in this pathway, could exist in at least two forms. One possessed little activity in the absence of glucose 6-phosphate (G6P), while the other was almost fully active in the absence of G6P.(1) Incubation of rat hemidiaphragms with insulin decreased the proportion of glycogen synthase in the G6P-dependent form which paralleled the increased rate of glycogen production.(1–3) Furthermore, the conversion of glycogen synthase to a G6Pindependent form was still observed when glucose was omitted from the perfusion medium,(2,3) indicating that it was not a consequence of the increased rate of transport of glucose into muscle, which is also stimulated by insulin. Conversely, incubation of the hemidiaphragms with epinephrine increased the proportion of the G6P-dependent form and decreased the rate of glycogen synthesis.(2,3)

Keywords

Activity Ratio Phosphate Content Glycogen Phosphorylase Rabbit Skeletal Muscle Phosphorylase Kinase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • Philip Cohen
    • 1
  • Peter J. Parker
    • 2
  • James R. Woodgett
    • 3
  1. 1.Department of BiochemistryUniversity of DundeeDundeeScotland
  2. 2.Imperial Cancer Research Fund LaboratoriesLondonEngland
  3. 3.Salk InstituteLa JollaUSA

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