A Limited Role for PI(3,4,5)P3 Regulation in Controlling Skeletal Muscle Mass in Response to Resistance Exercise
Open accessAbstract
BACKGROUND: Since activation of the PI3K/(protein kinase B; PKB/akt) pathway has been shown to alter muscle mass and growth, the aim of this study was to determine whether resistance exercise increased insulin like growth factor (IGF) I/phosphoinositide 3-kinase (PI3K) signalling and whether altering PI(3,4,5)P(3) metabolism genetically would increase load induced muscle growth. METHODOLOGY/PRINCIPAL FINDINGS: Acute and chronic resistance exercise in wild type and muscle specific PTEN knockout mice were used to address the role of PI(3,4,5)P(3) regulation in the development of skeletal muscle hypertrophy. Acute resistance exercise did not increase either IGF-1 receptor phosphorylation or IRS1/2 associated p85. Since insulin/IGF signalling to PI3K was unchanged, we next sought to determine whether inactivation of PTEN played a role in load-induced muscle growth. Muscle specific knockout of PTEN resulted in small but significant increases in heart (PTEN(+/+) = 5.00+/-0.02 mg/g, PTEN(-/-) = 5.50+/-0.09 mg/g), and TA (PTEN(+/+) = 1.74+/-0.04 mg/g, PTEN(-/-) = 1.89 +/-0.03) muscle mass, while the GTN, SOL, EDL and PLN remain unchanged. Following ablation, hypertrophy of the PLN, SOL or EDL muscles was similar between PTEN(-/-) and PTEN(+/+) animals. Even though there were some changes in overload-induced PKB and S6K1 phosphorylation, 1 hr following acute resistance exercise there was no difference in the phosphorylation state of S6K1 Thr389 between genotypes. CONCLUSIONS/SIGNIFICANCE: These data suggest that physiological loading does not lead to the enhanced activation of the PI3K/PKB/mTORC1 axis and that neither PI3K activation nor PTEN, and by extension PI(3,4,5)P(3) levels, play a significant role in adult skeletal muscle growth.
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Resistance exercise activates mTOR without activating PI3K.
“Unlike growth factors that use a receptor tyrosine kinase to signal through phosphoinositide 3-kinase (PI3K) to PKB, resistance exercise activates mTOR without activating PI3K [13].”
From Using Molecular Biology to Maximize Concurrent Training (2014) · cites this paper as [13]
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References 59 · Cited by 71
Research works printed but not linked: 2
- [40]McGee SL Mustard KJ Hardie DG Baar K 2008 Normal hypertrophy accompanied by phosphoryation and activation of AMP-activated protein kinase alpha1 following overload in LKB1 knockout mice. J Physiol 586 1731 1741 18202101 PMC2327866
- [44]Spangenburg EE Le Roith D Ward CW Bodine SC 2008 A functional insulin-like growth factor receptor is not necessary for load-induced skeletal muscle hypertrophy. J Physiol 586 283 291 17974583 PMC2375552
- Authors
- Hamilton, D. L., Philp, A., MacKenzie, M. G., & Baar, K.
- Affiliations
- University of Dundee (GB)
- Corresponding author
- Baar, Keith
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2010-07-16
- Volume
- 5
- Issue
- 7
- Pages
- e11624
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2905373
- OpenAlex
- W2042628823
- Cited by
- 71
- References
- 59
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 1 · 2021: 3 · 2020: 3 · 2019: 3 · 2018: 7 · 2017: 5 · 2016: 5 · 2015: 9 · 2014: 5 · 2013: 7 · 2012: 11
- FWCI
- 3.25
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Deakin Research Online (Deakin University) (submittedVersion)
- Stirling Online Research Repository (University of Stirling) (submittedVersion, cc-by)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- Wellcome Trust (077426)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- phosphatidylinositol 3,4,5-trisphosphate, phosphatidylinositol 3-kinase, PTEN, resistance training, skeletal muscle hypertrophy, muscle mass, IGF-1 signaling, S6K1 phosphorylation, muscle-specific knockout mice
- MeSH terms
- Animals, Female, Genotype, Immunohistochemistry, Male, Myocardium, Phosphatidylinositols, Phosphorylation, Stress, Mechanical, Blotting, Western, Receptor, IGF Type 1, Mice, Knockout, Muscle, Skeletal, Ribosomal Protein S6 Kinases, 90-kDa, PTEN Phosphohydrolase, Mice, In Vitro Techniques
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