Transforming Growth Factor Beta 1 Alters Glucose Uptake but Not Insulin Signalling in Human Primary Myotubes From Women With and Without Polycystic Ovary Syndrome
Women with polycystic ovary syndrome (PCOS), commonly have profound skeletal muscle insulin resistance which can worsen other clinical features. The heterogeneity of the condition has made it challenging to identify the precise mechanisms that cause this insulin resistance. A possible explanation fo...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2021.732338/full |
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| author | Luke C. McIlvenna Rhiannon K. Patten Andrew J. McAinch Andrew J. McAinch Raymond J. Rodgers Nigel K. Stepto Nigel K. Stepto Alba Moreno-Asso Alba Moreno-Asso |
| author_facet | Luke C. McIlvenna Rhiannon K. Patten Andrew J. McAinch Andrew J. McAinch Raymond J. Rodgers Nigel K. Stepto Nigel K. Stepto Alba Moreno-Asso Alba Moreno-Asso |
| author_sort | Luke C. McIlvenna |
| collection | DOAJ |
| description | Women with polycystic ovary syndrome (PCOS), commonly have profound skeletal muscle insulin resistance which can worsen other clinical features. The heterogeneity of the condition has made it challenging to identify the precise mechanisms that cause this insulin resistance. A possible explanation for the underlying insulin resistance may be the dysregulation of Transforming Growth Factor-beta (TGFβ) signalling. TGFβ signalling contributes to the remodelling of reproductive and hepatic tissues in women with PCOS. Given the systemic nature of TGFβ signalling and its role in skeletal muscle homeostasis, it may be possible that these adverse effects extend to other peripheral tissues. We aimed to determine if TGFβ1 could negatively regulate glucose uptake and insulin signalling in skeletal muscle of women with PCOS. We show that both myotubes from women with PCOS and healthy women displayed an increase in glucose uptake, independent of changes in insulin signalling, following short term (16 hr) TGFβ1 treatment. This increase occurred despite pro-fibrotic signalling increasing via SMAD3 and connective tissue growth factor in both groups following treatment with TGFβ1. Collectively, our findings show that short-term treatment with TGFβ1 does not appear to influence insulin signalling or promote insulin resistance in myotubes. These findings suggest that aberrant TGFβ signalling is unlikely to directly contribute to skeletal muscle insulin resistance in women with PCOS in the short term but does not rule out indirect or longer-term effects. |
| first_indexed | 2024-12-22T08:34:37Z |
| format | Article |
| id | doaj.art-9d9c499c7c684de8abbf2f02a6881717 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-12-22T08:34:37Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-9d9c499c7c684de8abbf2f02a68817172022-12-21T18:32:24ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922021-10-011210.3389/fendo.2021.732338732338Transforming Growth Factor Beta 1 Alters Glucose Uptake but Not Insulin Signalling in Human Primary Myotubes From Women With and Without Polycystic Ovary SyndromeLuke C. McIlvenna0Rhiannon K. Patten1Andrew J. McAinch2Andrew J. McAinch3Raymond J. Rodgers4Nigel K. Stepto5Nigel K. Stepto6Alba Moreno-Asso7Alba Moreno-Asso8Institute for Health and Sport, Victoria University, Melbourne, VIC, AustraliaInstitute for Health and Sport, Victoria University, Melbourne, VIC, AustraliaInstitute for Health and Sport, Victoria University, Melbourne, VIC, AustraliaAustralian Institute for Musculoskeletal Science (AIMSS), Victoria University, Melbourne, VIC, AustraliaDiscipline of Obstetrics and Gynaecology, School of Medicine, Robinson Research Institute, The University of Adelaide, Adelaide, SA, AustraliaInstitute for Health and Sport, Victoria University, Melbourne, VIC, AustraliaAustralian Institute for Musculoskeletal Science (AIMSS), Victoria University, Melbourne, VIC, AustraliaInstitute for Health and Sport, Victoria University, Melbourne, VIC, AustraliaAustralian Institute for Musculoskeletal Science (AIMSS), Victoria University, Melbourne, VIC, AustraliaWomen with polycystic ovary syndrome (PCOS), commonly have profound skeletal muscle insulin resistance which can worsen other clinical features. The heterogeneity of the condition has made it challenging to identify the precise mechanisms that cause this insulin resistance. A possible explanation for the underlying insulin resistance may be the dysregulation of Transforming Growth Factor-beta (TGFβ) signalling. TGFβ signalling contributes to the remodelling of reproductive and hepatic tissues in women with PCOS. Given the systemic nature of TGFβ signalling and its role in skeletal muscle homeostasis, it may be possible that these adverse effects extend to other peripheral tissues. We aimed to determine if TGFβ1 could negatively regulate glucose uptake and insulin signalling in skeletal muscle of women with PCOS. We show that both myotubes from women with PCOS and healthy women displayed an increase in glucose uptake, independent of changes in insulin signalling, following short term (16 hr) TGFβ1 treatment. This increase occurred despite pro-fibrotic signalling increasing via SMAD3 and connective tissue growth factor in both groups following treatment with TGFβ1. Collectively, our findings show that short-term treatment with TGFβ1 does not appear to influence insulin signalling or promote insulin resistance in myotubes. These findings suggest that aberrant TGFβ signalling is unlikely to directly contribute to skeletal muscle insulin resistance in women with PCOS in the short term but does not rule out indirect or longer-term effects.https://www.frontiersin.org/articles/10.3389/fendo.2021.732338/fullExtracellular matrixfibrosisinsulin resistanceskeletal muscleendocrinologycytokines |
| spellingShingle | Luke C. McIlvenna Rhiannon K. Patten Andrew J. McAinch Andrew J. McAinch Raymond J. Rodgers Nigel K. Stepto Nigel K. Stepto Alba Moreno-Asso Alba Moreno-Asso Transforming Growth Factor Beta 1 Alters Glucose Uptake but Not Insulin Signalling in Human Primary Myotubes From Women With and Without Polycystic Ovary Syndrome Frontiers in Endocrinology Extracellular matrix fibrosis insulin resistance skeletal muscle endocrinology cytokines |
| title | Transforming Growth Factor Beta 1 Alters Glucose Uptake but Not Insulin Signalling in Human Primary Myotubes From Women With and Without Polycystic Ovary Syndrome |
| title_full | Transforming Growth Factor Beta 1 Alters Glucose Uptake but Not Insulin Signalling in Human Primary Myotubes From Women With and Without Polycystic Ovary Syndrome |
| title_fullStr | Transforming Growth Factor Beta 1 Alters Glucose Uptake but Not Insulin Signalling in Human Primary Myotubes From Women With and Without Polycystic Ovary Syndrome |
| title_full_unstemmed | Transforming Growth Factor Beta 1 Alters Glucose Uptake but Not Insulin Signalling in Human Primary Myotubes From Women With and Without Polycystic Ovary Syndrome |
| title_short | Transforming Growth Factor Beta 1 Alters Glucose Uptake but Not Insulin Signalling in Human Primary Myotubes From Women With and Without Polycystic Ovary Syndrome |
| title_sort | transforming growth factor beta 1 alters glucose uptake but not insulin signalling in human primary myotubes from women with and without polycystic ovary syndrome |
| topic | Extracellular matrix fibrosis insulin resistance skeletal muscle endocrinology cytokines |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2021.732338/full |
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