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Effects of Cortisol and Dexamethasone on Insulin Signalling Pathways in Skeletal Muscle of the Ovine Fetus during Late Gestation

Before birth, glucocorticoids retard growth, although the extent to which this is mediated by changes in insulin signalling pathways in the skeletal muscle of the fetus is unknown. The current study determined the effects of endogenous and synthetic glucocorticoid exposure on insulin signalling prot...

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Autores principales: Jellyman, Juanita K., Martin-Gronert, Malgorzata S., Cripps, Roselle L., Giussani, Dino A., Ozanne, Susan E., Shen, Qingwu W., Du, Min, Fowden, Abigail L., Forhead, Alison J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3530600/
https://www.ncbi.nlm.nih.gov/pubmed/23300651
http://dx.doi.org/10.1371/journal.pone.0052363
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author Jellyman, Juanita K.
Martin-Gronert, Malgorzata S.
Cripps, Roselle L.
Giussani, Dino A.
Ozanne, Susan E.
Shen, Qingwu W.
Du, Min
Fowden, Abigail L.
Forhead, Alison J.
author_facet Jellyman, Juanita K.
Martin-Gronert, Malgorzata S.
Cripps, Roselle L.
Giussani, Dino A.
Ozanne, Susan E.
Shen, Qingwu W.
Du, Min
Fowden, Abigail L.
Forhead, Alison J.
author_sort Jellyman, Juanita K.
collection PubMed
description Before birth, glucocorticoids retard growth, although the extent to which this is mediated by changes in insulin signalling pathways in the skeletal muscle of the fetus is unknown. The current study determined the effects of endogenous and synthetic glucocorticoid exposure on insulin signalling proteins in skeletal muscle of fetal sheep during late gestation. Experimental manipulation of fetal plasma glucocorticoid concentration was achieved by fetal cortisol infusion and maternal dexamethasone treatment. Cortisol infusion significantly increased muscle protein levels of Akt2 and phosphorylated Akt at Ser473, and decreased protein levels of phosphorylated forms of mTOR at Ser2448 and S6K at Thr389. Muscle GLUT4 protein expression was significantly higher in fetuses whose mothers were treated with dexamethasone compared to those treated with saline. There were no significant effects of glucocorticoid exposure on muscle protein abundance of IR-β, IGF-1R, PKCζ, Akt1, calpastatin or muscle glycogen content. The present study demonstrated that components of the insulin signalling pathway in skeletal muscle of the ovine fetus are influenced differentially by naturally occurring and synthetic glucocorticoids. These findings may provide a mechanism by which elevated concentrations of endogenous glucocorticoids retard fetal growth.
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spelling pubmed-35306002013-01-08 Effects of Cortisol and Dexamethasone on Insulin Signalling Pathways in Skeletal Muscle of the Ovine Fetus during Late Gestation Jellyman, Juanita K. Martin-Gronert, Malgorzata S. Cripps, Roselle L. Giussani, Dino A. Ozanne, Susan E. Shen, Qingwu W. Du, Min Fowden, Abigail L. Forhead, Alison J. PLoS One Research Article Before birth, glucocorticoids retard growth, although the extent to which this is mediated by changes in insulin signalling pathways in the skeletal muscle of the fetus is unknown. The current study determined the effects of endogenous and synthetic glucocorticoid exposure on insulin signalling proteins in skeletal muscle of fetal sheep during late gestation. Experimental manipulation of fetal plasma glucocorticoid concentration was achieved by fetal cortisol infusion and maternal dexamethasone treatment. Cortisol infusion significantly increased muscle protein levels of Akt2 and phosphorylated Akt at Ser473, and decreased protein levels of phosphorylated forms of mTOR at Ser2448 and S6K at Thr389. Muscle GLUT4 protein expression was significantly higher in fetuses whose mothers were treated with dexamethasone compared to those treated with saline. There were no significant effects of glucocorticoid exposure on muscle protein abundance of IR-β, IGF-1R, PKCζ, Akt1, calpastatin or muscle glycogen content. The present study demonstrated that components of the insulin signalling pathway in skeletal muscle of the ovine fetus are influenced differentially by naturally occurring and synthetic glucocorticoids. These findings may provide a mechanism by which elevated concentrations of endogenous glucocorticoids retard fetal growth. Public Library of Science 2012-12-26 /pmc/articles/PMC3530600/ /pubmed/23300651 http://dx.doi.org/10.1371/journal.pone.0052363 Text en © 2012 Jellyman et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Jellyman, Juanita K.
Martin-Gronert, Malgorzata S.
Cripps, Roselle L.
Giussani, Dino A.
Ozanne, Susan E.
Shen, Qingwu W.
Du, Min
Fowden, Abigail L.
Forhead, Alison J.
Effects of Cortisol and Dexamethasone on Insulin Signalling Pathways in Skeletal Muscle of the Ovine Fetus during Late Gestation
title Effects of Cortisol and Dexamethasone on Insulin Signalling Pathways in Skeletal Muscle of the Ovine Fetus during Late Gestation
title_full Effects of Cortisol and Dexamethasone on Insulin Signalling Pathways in Skeletal Muscle of the Ovine Fetus during Late Gestation
title_fullStr Effects of Cortisol and Dexamethasone on Insulin Signalling Pathways in Skeletal Muscle of the Ovine Fetus during Late Gestation
title_full_unstemmed Effects of Cortisol and Dexamethasone on Insulin Signalling Pathways in Skeletal Muscle of the Ovine Fetus during Late Gestation
title_short Effects of Cortisol and Dexamethasone on Insulin Signalling Pathways in Skeletal Muscle of the Ovine Fetus during Late Gestation
title_sort effects of cortisol and dexamethasone on insulin signalling pathways in skeletal muscle of the ovine fetus during late gestation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3530600/
https://www.ncbi.nlm.nih.gov/pubmed/23300651
http://dx.doi.org/10.1371/journal.pone.0052363
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