A role for β-catenin in diet-induced skeletal muscle insulin resistance
Journal article
Mason, Stewart W. C., Dissanayake, Waruni C., Broome, Sophie C., Hedges, Christopher P., Peters, Wouter M., Gram, Martin, Rowlands, David S., Shepherd, Peter R. and Merry, Troy L.. (2023). A role for β-catenin in diet-induced skeletal muscle insulin resistance. Physiological Reports. 11(4), p. Article e15536. https://doi.org/10.14814/phy2.15536
Authors | Mason, Stewart W. C., Dissanayake, Waruni C., Broome, Sophie C., Hedges, Christopher P., Peters, Wouter M., Gram, Martin, Rowlands, David S., Shepherd, Peter R. and Merry, Troy L. |
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Abstract | A central characteristic of insulin resistance is the impaired ability for insulin to stimulate glucose uptake into skeletal muscle. While insulin resistance can occur distal to the canonical insulin receptor-PI3k-Akt signaling pathway, the signaling intermediates involved in the dysfunction are yet to be fully elucidated. β-catenin is an emerging distal regulator of skeletal muscle and adipocyte insulin-stimulated GLUT4 trafficking. Here, we investigate its role in skeletal muscle insulin resistance. Short-term (5-week) high-fat diet (HFD) decreased skeletal muscle β-catenin protein expression 27% (p = 0.03), and perturbed insulin-stimulated β-cateninS552 phosphorylation 21% (p = 0.009) without affecting insulin-stimulated Akt phosphorylation relative to chow-fed controls. Under chow conditions, mice with muscle-specific β-catenin deletion had impaired insulin responsiveness, whereas under HFD, both mice exhibited similar levels of insulin resistance (interaction effect of genotype × diet p < 0.05). Treatment of L6-GLUT4-myc myocytes with palmitate lower β-catenin protein expression by 75% (p = 0.02), and attenuated insulin-stimulated β-catenin phosphorylationS552 and actin remodeling (interaction effect of insulin × palmitate p < 0.05). Finally, β-cateninS552 phosphorylation was 45% lower in muscle biopsies from men with type 2 diabetes while total β-catenin expression was unchanged. These findings suggest that β-catenin dysfunction is associated with the development of insulin resistance. |
Keywords | glucose transport; insulin resistance; obesity; Wnt-signaling |
Year | 2023 |
Journal | Physiological Reports |
Journal citation | 11 (4), p. Article e15536 |
Publisher | Wiley Periodicals LLC |
ISSN | 2051-817X |
Digital Object Identifier (DOI) | https://doi.org/10.14814/phy2.15536 |
PubMed ID | 36807886 |
Scopus EID | 2-s2.0-85148588218 |
PubMed Central ID | PMC9937784 |
Open access | Published as ‘gold’ (paid) open access |
Page range | 1-13 |
Funder | Ministry of Business, Innovation and Employment (MBIE), Aotearoa New Zealand |
Royal Society Te Apārangi | |
University of Auckland | |
Publisher's version | License File Access Level Open |
Output status | Published |
Publication dates | |
Online | 17 Feb 2023 |
Publication process dates | |
Accepted | 20 Nov 2022 |
Deposited | 17 Nov 2023 |
Grant ID | UOOX1404 |
https://acuresearchbank.acu.edu.au/item/8zz3w/a-role-for-catenin-in-diet-induced-skeletal-muscle-insulin-resistance
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Publisher's version
OA_Mason_2023_A_role_for_β-catenin_in_diet-induced.pdf | |
License: CC BY 4.0 | |
File access level: Open |
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