Cited by 105Metabolism, Diabetes, and CancerGlycogen Storage Diseases and MyoclonusMuscle Physiology and Disorders

Increased glycogen accumulation in transgenic mice overexpressing glycogen synthase in skeletal muscle

Open access
Manchester, J, Skurat, A V, Roach, P, Hauschka, S D, Lawrence, J C·1996·Proceedings of the National Academy of Sciences

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.

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Crossref · 10.1073/pnas.93.20.10707

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Authors
Manchester, J., Skurat, A. V., Roach, P., Hauschka, S. D., & Lawrence, J. C.
Affiliations
Washington University in St. Louis (US)
Venue
Proceedings of the National Academy of Sciences
Published
1996-10
Volume
93
Issue
20
Pages
10707-10711
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2019612671
Cited by
105
References
45
Citations by year
2025: 1 · 2024: 4 · 2022: 3 · 2021: 1 · 2020: 2 · 2019: 3 · 2018: 1 · 2016: 4 · 2015: 3 · 2014: 1 · 2013: 2 · 2012: 5
FWCI
1.26
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Muscular Dystrophy Association
  • National Institutes of Health (1zicar041189-01)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK28312, DK 27221, R01DK028312)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR41189)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Health Sciences › Medicine › Rheumatology › Glycogen Storage Diseases and Myoclonus
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
Keywords
glycogen synthase, glycogen accumulation, skeletal muscle, transgenic mice, fast-twitch muscle, uridine diphosphoglucose, glycogen phosphorylase, glucose transporter 4, insulin signaling, glucose transport
MeSH terms
Animals, Glucose, Glycogen, Phosphorylases, Glycogen Synthase, Mice, Transgenic, Monosaccharide Transport Proteins, Muscle Proteins, Muscle, Skeletal, Glucose Transporter Type 4, Mice

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