β-Catenin is required for optimal exercise- andcontraction-stimulated skeletal muscle glucose uptake
Journal article
Masson, Stewart W. C., Woodhead, Jonathan S. T., D'Souza, Randall F., Broome, Sophie C., MacRae, Caitlin, Cho, Hyun C., Atiola, Robert D., Futi, Tumani, Dent, Jessica R., Shepherd, Peter R. and Merry, Troy L.. (2021). β-Catenin is required for optimal exercise- andcontraction-stimulated skeletal muscle glucose uptake. Journal of Physiology. 599(16), pp. 3897-3912. https://doi.org/10.1113/JP281352
Authors | Masson, Stewart W. C., Woodhead, Jonathan S. T., D'Souza, Randall F., Broome, Sophie C., MacRae, Caitlin, Cho, Hyun C., Atiola, Robert D., Futi, Tumani, Dent, Jessica R., Shepherd, Peter R. and Merry, Troy L. |
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Abstract | The conserved structural protein β-catenin is an emerging regulator of vesicle trafficking in multiple tissues and supports insulin-stimulated glucose transporter 4 (GLUT4) translocation in skeletal muscle by facilitating cortical actin remodelling. Actin remodelling may be a convergence point between insulin and exercise/contraction-stimulated glucose uptake. Here we investigated whether β-catenin is involved in regulating exercise/contraction-stimulated glucose uptake. We report that the muscle-specific deletion of β-catenin induced in adult mice (BCAT-mKO) impairs both exercise- and contraction (isolated muscle)-induced glucose uptake without affecting running performance or canonical exercise signalling pathways. Furthermore, high intensity exercise in mice and contraction of myotubes and isolated muscles led to the phosphorylation of β-cateninS675, and this was impaired by Rac1 inhibition. Moderate intensity exercise in control and Rac1 muscle-specific knockout mice did not induce muscle β-cateninS675 phosphorylation, suggesting exercise intensity-dependent regulation of β-cateninS675. Introduction of a non-phosphorylatable S675A mutant of β-catenin into myoblasts impaired GLUT4 translocation and actin remodelling stimulated by carbachol, a Rac1 and RhoA activator. Exercise-induced increases in cross-sectional phalloidin staining (F-actin marker) of gastrocnemius muscle was impaired in muscle from BCAT-mKO mice. Collectively our findings suggest that β-catenin is required for optimal glucose transport in muscle during exercise/contraction, potentially via facilitating actin cytoskeleton remodelling. |
Keywords | actin; glucose transport; GLUT4; insulin; Rac1 |
Year | 2021 |
Journal | Journal of Physiology |
Journal citation | 599 (16), pp. 3897-3912 |
Publisher | Wiley |
ISSN | 0022-3751 |
Digital Object Identifier (DOI) | https://doi.org/10.1113/JP281352 |
Scopus EID | 2-s2.0-85109790745 |
Page range | 3897-3912 |
Funder | Rutherford Discovery Fellowship |
University of Auckland | |
Publisher's version | License All rights reserved File Access Level Controlled |
Output status | Published |
Publication dates | |
Online | 27 Jun 2021 |
Publication process dates | |
Accepted | 22 Jun 2021 |
Deposited | 17 Jan 2023 |
https://acuresearchbank.acu.edu.au/item/8y9q7/-catenin-is-required-for-optimal-exercise-andcontraction-stimulated-skeletal-muscle-glucose-uptake
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