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Title: | Exercise and insulin resistance in PCOS: Muscle insulin signalling and fibrosis. | Authors: | Stepto N.K.;Moreno-Asso A.;Canny B.J.;Joham A.E.;Hutchison S.K.;Harrison C.L.;Cassar S.;Gibson-Helm M.;Hiam D.;Teede H.J. ;Rodgers R.J.;Hatzirodos N.;Strauss B.J. | Monash Health Department(s): | Diabetes and Vascular Medicine Endocrinology |
Institution: | (Stepto, Hiam, Cassar, Moreno-Asso) Institute for Health and Sport, Victoria University, Melbourne, VIC, Australia (Stepto, Gibson-Helm, Harrison, Hutchison, Joham, Teede) Monash Centre for Health Research and Implementation, Monash University, Clayton, VIC, Australia (Stepto, Moreno-Asso) Australian Institute for Musculoskeletal Science, Victoria University, Melbourne, VIC, Australia (Stepto) Medicine-Western Health, Faculty of Medicine, Dentistry and Health Science, Melbourne University, Melbourne, VIC, Australia (Canny) School of Medicine, University of Tasmania, Hobart, TAS, Australia (Strauss) Department of Medicine, School of Clinical Sciences, Monash University, Clayton, VIC, Australia (Strauss) Division of Diabetes, Endocrinology & Gastroenterology, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom (Hatzirodos, Rodgers) The Robinson Research Institute, School of Medicine, The University of Adelaide, Adelaide, Australia (Teede) Diabetes and Endocrine Units, Monash Health, Clayton, VIC, Australia | Issue Date: | 2-Sep-2020 | Copyright year: | 2020 | Publisher: | BioScientifica Ltd. (Euro House, 22 Apex Court, Woodlands, Bradley Stoke, Bristol BS32 4JT, United Kingdom) | Place of publication: | United Kingdom | Publication information: | Endocrine Connections. 9 (4) (pp 346-359), 2020. Date of Publication: 2020. | Journal: | Endocrine Connections | Abstract: | 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 beta (TGFbeta)-regulated tissue fibrosis. We also explored the impact of aerobic exercise on these molecular pathways. Method(s): 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 and 30 min into a euglycaemic-hyperinsulinaemic clamp pre and post training. Result(s): We found reduced signalling in PCOS of mechanistic target of rapamycin (mTOR). Exercise training augmented but did not completely rescue this signalling defect in women with PCOS. Genes in the TGFbeta 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. Conclusion(s): We provide new insights into defects in early insulin signalling, 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 TGFbeta ligand regulating a fibrosis in the PCOS-obesity synergy in insulin resistance and altered responses to exercise. Interestingly, there was little evidence for hyperandrogenism as a mechanism for insulin resistance.Copyright © 2020 The authors Published by Bioscientifica Ltd. | DOI: | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.1530/EC-19-0551 | ISSN: | 2049-3614 (electronic) | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/28866 | Type: | Article | Subjects: | collagen adiponectin Western blotting waist circumference skeletal muscle signal transduction epidermal growth factor collagen type 3 collagen type 1 aerobic exercise anthropometric parameters exercise fibrosis gene expression glucose homeostasis glucose transport hyperandrogenism immunoblotting insulin resistance insulin sensitivity insulin signaling menstrual cycle glucose transporter 4 insulin receptor substrate 1 leptin mammalian target of rapamycin muscle protein oxidized low density lipoprotein receptor 1 peroxisome proliferator activated receptor gamma protein kinase B Smad2 protein somatomedin C testosterone transforming growth factor beta transforming growth factor beta1 triacylglycerol RNA real time polymerase chain reaction protein phosphorylation ovary polycystic disease obesity |
Type of Clinical Study or Trial: | Observational study (cohort, case-control, cross sectional or survey) |
Appears in Collections: | Articles |
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