Cited by 106Muscle Physiology and DisordersGrowth Hormone and Insulin-like Growth FactorsMuscle metabolism and nutrition

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Insulin-like growth factor (IGF-I) induces myotube hypertrophy associated with an increase in anaerobic glycolysis in a clonal skeletal-muscle cell model

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SEMSARIAN, Christopher, SUTRAVE, Pramod, RICHMOND, David R., GRAHAM, Robert M.·1999·Biochemical Journal

DOI 10.1042/bj3390443PMC PMC1220176

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Abstract

Insulin-like growth factor-I (IGF-I) is an important autocrine/paracrine mediator of skeletal-muscle growth and development. To develop a definitive cultured cell model of skeletal-muscle hypertrophy, C2C12 cells were stably transfected with IGF-I and clonal lines developed and evaluated. Quantitative morphometric analysis showed that IGF-I-transfected myotubes had a larger area (2381±60 µm2 versus 1429±39 µm2; P< 0.0001) and a greater maximum width (21.4±0.6 µm versus 13.9±0.3 µm; P< 0.0001) than control C2C12 myotubes, independent of the number of cell nuclei per myotube. IGF-I-transfected myotubes had higher levels of protein synthesis but no difference in DNA synthesis when compared with control myotubes, indicating the development of hypertrophy rather than hyperplasia. Both lactate dehydrogenase and alanine aminotransferase activities were increased (3- and 5-fold respectively), and total lactate levels were higher (2.3-fold) in IGF-I-transfected compared with control myotubes, indicating an increase in anaerobic glycolysis in the hypertrophied myotubes. However, expression of genes involved in skeletal-muscle growth or hypertrophy in vivo, e.g. myocyte nuclear factor and myostatin, was not altered in the IGF-I myotubes. Finally, myotube hypertrophy could also be induced by treatment of C2C12 cells with recombinant IGF-I or by growing C2C12 cells in conditioned media from IGF-I-transfected cells. This quantitative model should be uniquely useful for elucidating the molecular mechanisms of skeletal-muscle hypertrophy.

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Authors: SEMSARIAN, C., SUTRAVE, P., RICHMOND, D. R., & GRAHAM, R. M.
Affiliations: Victor Chang Cardiac Research Institute (AU)
Royal Prince Alfred Hospital (AU)
Corresponding author: SEMSARIAN, Christopher
SUTRAVE, Pramod
ORCID: SEMSARIAN, Christopher
GRAHAM, Robert M.
Venue: Biochemical Journal
Publisher: Portland Press Ltd.
Published: 1999-04-08
Volume: 339
Issue: 2
Pages: 443-451
ISSN: 0264-6021 (ISSN-L)
1470-8728
DOI: 10.1042/bj3390443
PMC: PMC1220176
OpenAlex: W2120432317
Cited by: 106
References: 46
Citations by year: 2026: 3 · 2024: 2 · 2023: 4 · 2022: 2 · 2021: 4 · 2020: 4 · 2018: 4 · 2017: 3 · 2016: 4 · 2015: 4 · 2014: 1 · 2013: 3 · 2012: 1
FWCI: 2.87
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Biochemical Journal (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Australian Government
Medical Research Council
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
Keywords: insulin-like growth factor I, skeletal muscle hypertrophy, myotube hypertrophy, anaerobic glycolysis, C2C12 myoblasts, stable transfection, protein synthesis, lactate dehydrogenase, alanine aminotransferase, myostatin, muscle growth
MeSH terms: Animals, Base Sequence, Cell Differentiation, Cell Division, Cell Line, DNA Replication, Glycolysis, Hypertrophy, Insulin-Like Growth Factor I, Models, Biological, RNA, Messenger, Transfection, DNA Primers, Muscle, Skeletal, Mice

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Insulin-like growth factor (IGF-I) induces myotube hypertrophy associated with an increase in anaerobic glycolysis in a clonal skeletal-muscle cell model

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