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

Masson SWC; Dissanayake WC; Broome SC; Hedges CP; Peeters WM; Gram M; Rowlands DS; Shepherd PR; Merry TL

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

dc.citation.issue	4
dc.citation.volume	11
dc.contributor.author	Masson SWC
dc.contributor.author	Dissanayake WC
dc.contributor.author	Broome SC
dc.contributor.author	Hedges CP
dc.contributor.author	Peeters WM
dc.contributor.author	Gram M
dc.contributor.author	Rowlands DS
dc.contributor.author	Shepherd PR
dc.contributor.author	Merry TL
dc.coverage.spatial	United States
dc.date.accessioned	2024-06-17T19:55:14Z
dc.date.available	2024-06-17T19:55:14Z
dc.date.issued	2023-02-17
dc.description.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.
dc.description.confidential	false
dc.edition.edition	Feb 2023
dc.format.pagination	e15536-
dc.identifier.author-url	https://www.ncbi.nlm.nih.gov/pubmed/36807886
dc.identifier.citation	Masson SWC, Dissanayake WC, Broome SC, Hedges CP, Peeters WM, Gram M, Rowlands DS, Shepherd PR, Merry TL. (2023). A role for β-catenin in diet-induced skeletal muscle insulin resistance.. Physiol Rep. 11. 4. (pp. e15536-).
dc.identifier.doi	10.14814/phy2.15536
dc.identifier.eissn	2051-817X
dc.identifier.elements-type	journal-article
dc.identifier.issn	2051-817X
dc.identifier.number	e15536
dc.identifier.uri	https://mro.massey.ac.nz/handle/10179/69872
dc.language	eng
dc.publisher	Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society
dc.publisher.uri	https://physoc.onlinelibrary.wiley.com/doi/10.14814/phy2.15536
dc.relation.isPartOf	Physiol Rep
dc.rights	(c) 2023 The Author/s
dc.rights	CC BY 4.0
dc.rights.uri	https://creativecommons.org/licenses/by/4.0/
dc.subject	Wnt-signaling
dc.subject	glucose transport
dc.subject	insulin resistance
dc.subject	obesity
dc.subject	Mice
dc.subject	Animals
dc.subject	Insulin Resistance
dc.subject	Proto-Oncogene Proteins c-akt
dc.subject	Diabetes Mellitus, Type 2
dc.subject	Phosphatidylinositol 3-Kinases
dc.subject	beta Catenin
dc.subject	Glucose
dc.subject	Muscle, Skeletal
dc.subject	Insulin
dc.subject	Diet, High-Fat
dc.subject	Phosphorylation
dc.subject	Glucose Transporter Type 4
dc.title	A role for β-catenin in diet-induced skeletal muscle insulin resistance.
dc.type	Journal article
pubs.elements-id	459830
pubs.organisational-group	College of Health