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Perspectives in Diabetes

New Insights Into the Role and Mechanism of Glycogen Synthase Activation by Insulin

  1. John C Lawrence Jr and
  2. Peter J Roach
  1. Departments of Pharmacology and Medicine (J.C.L.), University of Virginia School of Medicine Charlottesville, Virginia
  2. Department of Biochemistry and Molecular Biology (P.J.R.), Indiana University School of Medicine Indianapolis, Indiana
  1. Address correspondence and reprint requests to Dr. John C. Lawrence, Jr., Department of Pharmacology, University of Virginia School of Medicine, Jordan Building, 1300 Jefferson Park Ave., Charlottesville, VA 22908. jcl3p{at}avery.med.virginia.edu.
Diabetes 1997 Apr; 46(4): 541-547. https://doi.org/10.2337/diab.46.4.541
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Abstract

The metabolism of the storage polysaccharide glycogen is intimately linked with insulin action and blood glucose homeostasis. Insulin activates both glucose transport and glycogen synthase in skeletal muscle. The central issue of a long-standing debate is which of these two effects determines the rate of glycogen synthesis in response to insulin. Recent studies with transgenic animals indicate that, under appropriate conditions, each process can contribute to determining the extent of glycogen accumulation. Insulin causes stable activation of glycogen synthase by promoting dephosphorylation of multiple sites in the enzyme. A model linking this action to the mitogen-activated protein kinase signaling pathway via the phosphorylation of the regulatory subunit of glycogen synthase phosphatase gained widespread acceptance. However, the most recent evidence argues strongly against this mechanism. A newer model, in which insulin inactivates the enzyme glycogen synthase kinase-3 via the protein kinase B pathway, has emerged. Though promising, this model still does not completely explain the molecular basis for the insulin-mediated activation of glycogen synthase, which remains one of the many unknowns of insulin action.

  • Received October 30, 1996.
  • Revision received January 29, 1997.
  • Accepted January 29, 1997.
  • Copyright © 1997 by the American Diabetes Association

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April 1997, 46(4)
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New Insights Into the Role and Mechanism of Glycogen Synthase Activation by Insulin
John C Lawrence, Peter J Roach
Diabetes Apr 1997, 46 (4) 541-547; DOI: 10.2337/diab.46.4.541

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New Insights Into the Role and Mechanism of Glycogen Synthase Activation by Insulin
John C Lawrence, Peter J Roach
Diabetes Apr 1997, 46 (4) 541-547; DOI: 10.2337/diab.46.4.541
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