A role for β‐catenin in diet‐induced skeletal muscle insulin resistance
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 dysfunctio...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-02-01
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| Series: | Physiological Reports |
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| Online Access: | https://doi.org/10.14814/phy2.15536 |
| _version_ | 1797397591900553216 |
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| author | Stewart W. C. Masson Waruni C. Dissanayake Sophie C. Broome Christopher P. Hedges Wouter M. Peeters Martin Gram David S. Rowlands Peter R. Shepherd Troy L. Merry |
| author_facet | Stewart W. C. Masson Waruni C. Dissanayake Sophie C. Broome Christopher P. Hedges Wouter M. Peeters Martin Gram David S. Rowlands Peter R. Shepherd Troy L. Merry |
| author_sort | Stewart W. C. Masson |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T01:12:19Z |
| format | Article |
| id | doaj.art-0f3992d53ffb40488d95e17febf0a71a |
| institution | Directory Open Access Journal |
| issn | 2051-817X |
| language | English |
| last_indexed | 2024-03-09T01:12:19Z |
| publishDate | 2023-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Physiological Reports |
| spelling | doaj.art-0f3992d53ffb40488d95e17febf0a71a2023-12-11T03:15:45ZengWileyPhysiological Reports2051-817X2023-02-01114n/an/a10.14814/phy2.15536A role for β‐catenin in diet‐induced skeletal muscle insulin resistanceStewart W. C. Masson0Waruni C. Dissanayake1Sophie C. Broome2Christopher P. Hedges3Wouter M. Peeters4Martin Gram5David S. Rowlands6Peter R. Shepherd7Troy L. Merry8Discipline of Nutrition, Faculty of Medical and Health Sciences The University of Auckland Auckland New ZealandMaurice Wilkins Centre for Molecular Biodiscovery The University of Auckland Auckland New ZealandDiscipline of Nutrition, Faculty of Medical and Health Sciences The University of Auckland Auckland New ZealandDiscipline of Nutrition, Faculty of Medical and Health Sciences The University of Auckland Auckland New ZealandSchool of Sport, Exercise and Nutrition Massey University Auckland New ZealandSchool of Sport, Exercise and Nutrition Massey University Auckland New ZealandSchool of Sport, Exercise and Nutrition Massey University Auckland New ZealandMaurice Wilkins Centre for Molecular Biodiscovery The University of Auckland Auckland New ZealandDiscipline of Nutrition, Faculty of Medical and Health Sciences The University of Auckland Auckland New ZealandAbstract 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.https://doi.org/10.14814/phy2.15536glucose transportinsulin resistanceobesityWnt‐signaling |
| spellingShingle | Stewart W. C. Masson Waruni C. Dissanayake Sophie C. Broome Christopher P. Hedges Wouter M. Peeters Martin Gram David S. Rowlands Peter R. Shepherd Troy L. Merry A role for β‐catenin in diet‐induced skeletal muscle insulin resistance Physiological Reports glucose transport insulin resistance obesity Wnt‐signaling |
| title | A role for β‐catenin in diet‐induced skeletal muscle insulin resistance |
| title_full | A role for β‐catenin in diet‐induced skeletal muscle insulin resistance |
| title_fullStr | A role for β‐catenin in diet‐induced skeletal muscle insulin resistance |
| title_full_unstemmed | A role for β‐catenin in diet‐induced skeletal muscle insulin resistance |
| title_short | A role for β‐catenin in diet‐induced skeletal muscle insulin resistance |
| title_sort | role for β catenin in diet induced skeletal muscle insulin resistance |
| topic | glucose transport insulin resistance obesity Wnt‐signaling |
| url | https://doi.org/10.14814/phy2.15536 |
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