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A role for β-catenin in diet-induced skeletal muscle insulin resistance

Lookup NU author(s): Wouter PeetersORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2023 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.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.


Publication metadata

Author(s): Masson SWC, Dissanayake WC, Broome SC, Hedges CP, Peeters WM, Gram M, Rowlands DS, Shepherd PR, Merry TL

Publication type: Article

Publication status: Published

Journal: Physiological Reports

Year: 2023

Volume: 11

Issue: 4

Print publication date: 01/02/2023

Online publication date: 17/02/2023

Acceptance date: 20/11/2022

Date deposited: 07/03/2023

ISSN (print): 2051-817X

Publisher: American Physiological Society

URL: https://doi.org/10.14814/phy2.15536

DOI: 10.14814/phy2.15536

PubMed id: 36807886


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Funding

Funder referenceFunder name
UOOX1404

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