Increased glycogen accumulation in transgenic mice overexpressing glycogen synthase in skeletal muscle
Open accessAbstract
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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- Authors
- Manchester, J., Skurat, A. V., Roach, P., Hauschka, S. D., & Lawrence, J. C.
- Affiliations
- Washington University in St. Louis (US)
- ORCID
- Hauschka, S D
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1996-10
- Volume
- 93
- Issue
- 20
- Pages
- 10707-10711
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC38219
- 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
- green
- www.ncbi.nlm.nih.gov
- 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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