Effect of insulin insufficiency on ultrastructure and function in skeletal muscle
Abstract Background Decreased insulin availability and high blood glucose levels, the hallmark features of poorly controlled diabetes, drive disease progression and are associated with decreased skeletal muscle mass. We have shown that mice with β‐cell dysfunction and normal insulin sensitivity have...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2024-02-01
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| Series: | Journal of Cachexia, Sarcopenia and Muscle |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/jcsm.13380 |
| _version_ | 1797335213106266112 |
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| author | Chantal Kopecky Michael Haug Barbara Reischl Nandan Deshpande Bikash Manandhar Thomas W. King Victoria Lee Marc R. Wilkins Margaret Morris Patsie Polly Oliver Friedrich Kerry‐Anne Rye Blake J. Cochran |
| author_facet | Chantal Kopecky Michael Haug Barbara Reischl Nandan Deshpande Bikash Manandhar Thomas W. King Victoria Lee Marc R. Wilkins Margaret Morris Patsie Polly Oliver Friedrich Kerry‐Anne Rye Blake J. Cochran |
| author_sort | Chantal Kopecky |
| collection | DOAJ |
| description | Abstract Background Decreased insulin availability and high blood glucose levels, the hallmark features of poorly controlled diabetes, drive disease progression and are associated with decreased skeletal muscle mass. We have shown that mice with β‐cell dysfunction and normal insulin sensitivity have decreased skeletal muscle mass. This project asks how insulin deficiency impacts on the structure and function of the remaining skeletal muscle in these animals. Methods Skeletal muscle function was determined by measuring exercise capacity and specific muscle strength prior to and after insulin supplementation for 28 days in 12‐week‐old mice with conditional β‐cell deletion of the ATP binding cassette transporters ABCA1 and ABCG1 (β‐DKO mice). Abca1 and Abcg1 floxed (fl/fl) mice were used as controls. RNAseq was used to quantify changes in transcripts in soleus and extensor digitorum longus muscles. Skeletal muscle and mitochondrial morphology were assessed by transmission electron microscopy. Myofibrillar Ca2+ sensitivity and maximum isometric single muscle fibre force were assessed using MyoRobot biomechatronics technology. Results RNA transcripts were significantly altered in β‐DKO mice compared with fl/fl controls (32 in extensor digitorum longus and 412 in soleus). Exercise capacity and muscle strength were significantly decreased in β‐DKO mice compared with fl/fl controls (P = 0.012), and a loss of structural integrity was also observed in skeletal muscle from the β‐DKO mice. Supplementation of β‐DKO mice with insulin restored muscle integrity, strength and expression of 13 and 16 of the dysregulated transcripts in and extensor digitorum longus and soleus muscles, respectively. Conclusions Insulin insufficiency due to β‐cell dysfunction perturbs the structure and function of skeletal muscle. These adverse effects are rectified by insulin supplementation. |
| first_indexed | 2024-03-08T08:33:40Z |
| format | Article |
| id | doaj.art-c9be2adfa87a4331a6dbb7b63f6da60b |
| institution | Directory Open Access Journal |
| issn | 2190-5991 2190-6009 |
| language | English |
| last_indexed | 2024-03-08T08:33:40Z |
| publishDate | 2024-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Cachexia, Sarcopenia and Muscle |
| spelling | doaj.art-c9be2adfa87a4331a6dbb7b63f6da60b2024-02-02T02:28:29ZengWileyJournal of Cachexia, Sarcopenia and Muscle2190-59912190-60092024-02-0115111212310.1002/jcsm.13380Effect of insulin insufficiency on ultrastructure and function in skeletal muscleChantal Kopecky0Michael Haug1Barbara Reischl2Nandan Deshpande3Bikash Manandhar4Thomas W. King5Victoria Lee6Marc R. Wilkins7Margaret Morris8Patsie Polly9Oliver Friedrich10Kerry‐Anne Rye11Blake J. Cochran12School of Biomedical Sciences, Faculty of Medicine & Health UNSW Sydney Sydney AustraliaDepartment of Chemical and Biological Engineering, Institute of Medical Biotechnology Friedrich‐Alexander University Erlangen‐Nürnberg Erlangen GermanyDepartment of Chemical and Biological Engineering, Institute of Medical Biotechnology Friedrich‐Alexander University Erlangen‐Nürnberg Erlangen GermanySydney Informatics Hub University of Sydney Sydney AustraliaSchool of Biomedical Sciences, Faculty of Medicine & Health UNSW Sydney Sydney AustraliaSchool of Biomedical Sciences, Faculty of Medicine & Health UNSW Sydney Sydney AustraliaSchool of Biomedical Sciences, Faculty of Medicine & Health UNSW Sydney Sydney AustraliaSystems Biology Initiative, Faculty of Science UNSW Sydney Sydney AustraliaSchool of Biomedical Sciences, Faculty of Medicine & Health UNSW Sydney Sydney AustraliaSchool of Biomedical Sciences, Faculty of Medicine & Health UNSW Sydney Sydney AustraliaSchool of Biomedical Sciences, Faculty of Medicine & Health UNSW Sydney Sydney AustraliaSchool of Biomedical Sciences, Faculty of Medicine & Health UNSW Sydney Sydney AustraliaSchool of Biomedical Sciences, Faculty of Medicine & Health UNSW Sydney Sydney AustraliaAbstract Background Decreased insulin availability and high blood glucose levels, the hallmark features of poorly controlled diabetes, drive disease progression and are associated with decreased skeletal muscle mass. We have shown that mice with β‐cell dysfunction and normal insulin sensitivity have decreased skeletal muscle mass. This project asks how insulin deficiency impacts on the structure and function of the remaining skeletal muscle in these animals. Methods Skeletal muscle function was determined by measuring exercise capacity and specific muscle strength prior to and after insulin supplementation for 28 days in 12‐week‐old mice with conditional β‐cell deletion of the ATP binding cassette transporters ABCA1 and ABCG1 (β‐DKO mice). Abca1 and Abcg1 floxed (fl/fl) mice were used as controls. RNAseq was used to quantify changes in transcripts in soleus and extensor digitorum longus muscles. Skeletal muscle and mitochondrial morphology were assessed by transmission electron microscopy. Myofibrillar Ca2+ sensitivity and maximum isometric single muscle fibre force were assessed using MyoRobot biomechatronics technology. Results RNA transcripts were significantly altered in β‐DKO mice compared with fl/fl controls (32 in extensor digitorum longus and 412 in soleus). Exercise capacity and muscle strength were significantly decreased in β‐DKO mice compared with fl/fl controls (P = 0.012), and a loss of structural integrity was also observed in skeletal muscle from the β‐DKO mice. Supplementation of β‐DKO mice with insulin restored muscle integrity, strength and expression of 13 and 16 of the dysregulated transcripts in and extensor digitorum longus and soleus muscles, respectively. Conclusions Insulin insufficiency due to β‐cell dysfunction perturbs the structure and function of skeletal muscle. These adverse effects are rectified by insulin supplementation.https://doi.org/10.1002/jcsm.13380InsulinMuscle functionMuscle structureSkeletal muscle |
| spellingShingle | Chantal Kopecky Michael Haug Barbara Reischl Nandan Deshpande Bikash Manandhar Thomas W. King Victoria Lee Marc R. Wilkins Margaret Morris Patsie Polly Oliver Friedrich Kerry‐Anne Rye Blake J. Cochran Effect of insulin insufficiency on ultrastructure and function in skeletal muscle Journal of Cachexia, Sarcopenia and Muscle Insulin Muscle function Muscle structure Skeletal muscle |
| title | Effect of insulin insufficiency on ultrastructure and function in skeletal muscle |
| title_full | Effect of insulin insufficiency on ultrastructure and function in skeletal muscle |
| title_fullStr | Effect of insulin insufficiency on ultrastructure and function in skeletal muscle |
| title_full_unstemmed | Effect of insulin insufficiency on ultrastructure and function in skeletal muscle |
| title_short | Effect of insulin insufficiency on ultrastructure and function in skeletal muscle |
| title_sort | effect of insulin insufficiency on ultrastructure and function in skeletal muscle |
| topic | Insulin Muscle function Muscle structure Skeletal muscle |
| url | https://doi.org/10.1002/jcsm.13380 |
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