Exercise and insulin resistance in PCOS: muscle insulin signalling and fibrosis
Objective: Mechanisms of insulin resistance in polycystic ovary syndrome (PCOS) remain ill defined, contributing to sub-optimal therapies. Recognising skeletal muscle plays a key role in glucose homeostasis we investigated early insulin signalling, its association with aberrant transforming growth f...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Bioscientifica
2020-04-01
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| Series: | Endocrine Connections |
| Subjects: | |
| Online Access: | https://ec.bioscientifica.com/view/journals/ec/9/4/EC-19-0551.xml |
| _version_ | 1818063661206339584 |
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| author | N K Stepto D Hiam M Gibson-Helm S Cassar C L Harrison S K Hutchison A E Joham B J Canny A Moreno-Asso B J Strauss N Hatzirodos R J Rodgers H J Teede |
| author_facet | N K Stepto D Hiam M Gibson-Helm S Cassar C L Harrison S K Hutchison A E Joham B J Canny A Moreno-Asso B J Strauss N Hatzirodos R J Rodgers H J Teede |
| author_sort | N K Stepto |
| collection | DOAJ |
| description | Objective: Mechanisms of insulin resistance in polycystic ovary syndrome (PCOS) remain ill defined, contributing to sub-optimal therapies. Recognising skeletal muscle plays a key role in glucose homeostasis we investigated early insulin signalling, its association with aberrant transforming growth factor β (TGFβ)-regulated tissue fibrosis. We also explored the impact of aerobic exercise on these molecular pathways.
Methods: A secondary analysis from a cross-sectional study was undertaken in women with (n = 30) or without (n = 29) PCOS across lean and overweight BMIs. A subset of participants with (n = 8) or without (n = 8) PCOS who were overweight completed 12 weeks of aerobic exercise training. Muscle was sampled before a nd 30 min into a euglycaemic-hyperinsulinaemic clamp pre and post training.
Results: We found reduced signalling in PCOS of mechanistic target of r apamycin (mTOR). Exercise training augmented but did not completely rescue this signalling defect in women with PCOS. Genes in the TGFβ signalling network were upregulated in skeletal muscle in the overweight women with PCOS but were unresponsive to exercise training except for genes encoding LOX, collagen 1 and 3.
Conclusions: We provide new insights into defects in early insulin signalli ng, tissue fibrosis, and hyperandrogenism in PCOS-specific insulin resistance in lean and overweight women. PCOS-specific insulin signalling defects were isolated to mTOR, while gene expression implicated TGFβ ligand regulating a fibrosis in the PCOS-obesity synergy in ins ulin resistance and altered responses to exercise. Interestingly, th ere was little evidence for hyperandrogenism as a mechanism for insulin resistance. |
| first_indexed | 2024-12-10T14:23:39Z |
| format | Article |
| id | doaj.art-a3481e1c1ddb433ab251a514d68a2e2f |
| institution | Directory Open Access Journal |
| issn | 2049-3614 2049-3614 |
| language | English |
| last_indexed | 2024-12-10T14:23:39Z |
| publishDate | 2020-04-01 |
| publisher | Bioscientifica |
| record_format | Article |
| series | Endocrine Connections |
| spelling | doaj.art-a3481e1c1ddb433ab251a514d68a2e2f2022-12-22T01:45:07ZengBioscientificaEndocrine Connections2049-36142049-36142020-04-0194346359https://doi.org/10.1530/EC-19-0551Exercise and insulin resistance in PCOS: muscle insulin signalling and fibrosisN K Stepto0D Hiam1M Gibson-Helm2S Cassar3C L Harrison4S K Hutchison5A E Joham6B J Canny7A Moreno-Asso8B J Strauss9N Hatzirodos10R J Rodgers11H J Teede12Institute for Health and Sport, Victoria University, Melbourne, Victoria, Australia; Monash Centre for Health Research and Implementation, Monash University, Clayton, Victoria, Australia; Australian Institute for Musculoskeletal Science, Victoria University, Melbourne, Victoria, Australia; Medicine-Western Health, Faculty of Medicine, Dentistry and Health Science, Melbourne University, Melbourne, Victoria, AustraliaInstitute for Health and Sport, Victoria University, Melbourne, Victoria, AustraliaMonash Centre for Health Research and Implementation, Monash University, Clayton, Victoria, AustraliaInstitute for Health and Sport, Victoria University, Melbourne, Victoria, AustraliaMonash Centre for Health Research and Implementation, Monash University, Clayton, Victoria, AustraliaMonash Centre for Health Research and Implementation, Monash University, Clayton, Victoria, AustraliaMonash Centre for Health Research and Implementation, Monash University, Clayton, Victoria, AustraliaSchool of Medicine, University of Tasmania, Hobart, Tasmania, AustraliaInstitute for Health and Sport, Victoria University, Melbourne, Victoria, Australia; Australian Institute for Musculoskeletal Science, Victoria University, Melbourne, Victoria, AustraliaDepartment of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia; Division of Diabetes, Endocrinology & Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UKThe Robinson Research Institute, School of Medicine, The University of Adelaide, Adelaide, AustraliaThe Robinson Research Institute, School of Medicine, The University of Adelaide, Adelaide, AustraliaMonash Centre for Health Research and Implementation, Monash University, Clayton, Victoria, Australia; Diabetes and Endocrine Units, Monash Health, Clayton, Victoria, AustraliaObjective: Mechanisms of insulin resistance in polycystic ovary syndrome (PCOS) remain ill defined, contributing to sub-optimal therapies. Recognising skeletal muscle plays a key role in glucose homeostasis we investigated early insulin signalling, its association with aberrant transforming growth factor β (TGFβ)-regulated tissue fibrosis. We also explored the impact of aerobic exercise on these molecular pathways. Methods: A secondary analysis from a cross-sectional study was undertaken in women with (n = 30) or without (n = 29) PCOS across lean and overweight BMIs. A subset of participants with (n = 8) or without (n = 8) PCOS who were overweight completed 12 weeks of aerobic exercise training. Muscle was sampled before a nd 30 min into a euglycaemic-hyperinsulinaemic clamp pre and post training. Results: We found reduced signalling in PCOS of mechanistic target of r apamycin (mTOR). Exercise training augmented but did not completely rescue this signalling defect in women with PCOS. Genes in the TGFβ signalling network were upregulated in skeletal muscle in the overweight women with PCOS but were unresponsive to exercise training except for genes encoding LOX, collagen 1 and 3. Conclusions: We provide new insights into defects in early insulin signalli ng, tissue fibrosis, and hyperandrogenism in PCOS-specific insulin resistance in lean and overweight women. PCOS-specific insulin signalling defects were isolated to mTOR, while gene expression implicated TGFβ ligand regulating a fibrosis in the PCOS-obesity synergy in ins ulin resistance and altered responses to exercise. Interestingly, th ere was little evidence for hyperandrogenism as a mechanism for insulin resistance.https://ec.bioscientifica.com/view/journals/ec/9/4/EC-19-0551.xmlmechanistic target of rapamysin (mtor)typical and atypical protein kinase ctransforming growth factor β receptor 2 (tgfbrii)collagentreadmill exercise traininghigh intensity interval traininghyperandrogenism |
| spellingShingle | N K Stepto D Hiam M Gibson-Helm S Cassar C L Harrison S K Hutchison A E Joham B J Canny A Moreno-Asso B J Strauss N Hatzirodos R J Rodgers H J Teede Exercise and insulin resistance in PCOS: muscle insulin signalling and fibrosis Endocrine Connections mechanistic target of rapamysin (mtor) typical and atypical protein kinase c transforming growth factor β receptor 2 (tgfbrii) collagen treadmill exercise training high intensity interval training hyperandrogenism |
| title | Exercise and insulin resistance in PCOS: muscle insulin signalling and fibrosis |
| title_full | Exercise and insulin resistance in PCOS: muscle insulin signalling and fibrosis |
| title_fullStr | Exercise and insulin resistance in PCOS: muscle insulin signalling and fibrosis |
| title_full_unstemmed | Exercise and insulin resistance in PCOS: muscle insulin signalling and fibrosis |
| title_short | Exercise and insulin resistance in PCOS: muscle insulin signalling and fibrosis |
| title_sort | exercise and insulin resistance in pcos muscle insulin signalling and fibrosis |
| topic | mechanistic target of rapamysin (mtor) typical and atypical protein kinase c transforming growth factor β receptor 2 (tgfbrii) collagen treadmill exercise training high intensity interval training hyperandrogenism |
| url | https://ec.bioscientifica.com/view/journals/ec/9/4/EC-19-0551.xml |
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