New insights into the role and mechanism of glycogen synthase activation by insulin

John C. Lawrence, Peter Roach

Research output: Contribution to journalArticle

262 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)541-547
Number of pages7
JournalDiabetes
Volume46
Issue number4
StatePublished - Apr 1997

Fingerprint

Glycogen Synthase
Insulin
Glycogen
Glycogen Synthase Kinase 3
Proto-Oncogene Proteins c-akt
Genetically Modified Animals
Enzymes
Mitogen-Activated Protein Kinases
Phosphoric Monoester Hydrolases
Polysaccharides
Blood Glucose
Skeletal Muscle
Homeostasis
Phosphorylation
Glucose

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

New insights into the role and mechanism of glycogen synthase activation by insulin. / Lawrence, John C.; Roach, Peter.

In: Diabetes, Vol. 46, No. 4, 04.1997, p. 541-547.

Research output: Contribution to journalArticle

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