Increased glycogen accumulation in transgenic mice over expressing glycogen synthase in skeletal muscle

Jill Manchester, Alexander Skurat, Peter Roach, Stephen D. Hauschka, John C. Lawrence

Research output: Contribution to journalArticle

84 Citations (Scopus)

Abstract

To investigate the role of glycogen synthase in controlling glycogen accumulation, we generated three lines of transgenic mice in which the enzyme was overexpressed in skeletal muscle by using promoter-enhancer elements derived from the mouse muscle creatine kinase gene. In all three lines, expression was highest in muscles composed primarily of fast-twitch fibers, such as the gastrocnemius and anterior tibialis. In these muscles, glycogen synthase activity was increased by as much as 10-fold, with concomitant increases (up to 5-fold) in the glycogen content. The uridine diphosphoglucose concentrations were markedly decreased, consistent with the increase in glycogen synthase activity. Levels of glycogen phosphorylase in these muscles increased (up to 3-fold), whereas the amount of the insulin-sensitive glucose transporter 4 either remained unchanged or decreased. The observation that increasing glycogen synthase enhances glycogen accumulation supports the conclusion that the activation of glycogen synthase, as well as glucose transport, contributes to the accumulation of glycogen in response to insulin in skeletal muscle.

Original languageEnglish
Pages (from-to)10707-10711
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number20
StatePublished - Oct 1 1996

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Glycogen Synthase
Glycogen
Transgenic Mice
Skeletal Muscle
Muscles
MM Form Creatine Kinase
Insulin
Uridine Diphosphate Glucose
Glycogen Phosphorylase
Facilitative Glucose Transport Proteins
Glucose
Enzymes
Genes

ASJC Scopus subject areas

  • General
  • Genetics

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Increased glycogen accumulation in transgenic mice over expressing glycogen synthase in skeletal muscle. / Manchester, Jill; Skurat, Alexander; Roach, Peter; Hauschka, Stephen D.; Lawrence, John C.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 93, No. 20, 01.10.1996, p. 10707-10711.

Research output: Contribution to journalArticle

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