There is increasing evidence that miRNAs, which are enriched in nanovesicles called exosomes, are important regulators of gene expression. When compared with normal pregnancies, pregnancies with gestational diabetes mellitus (GDM) are associated with skeletal muscle insulin resistance as well as increased levels of circulating placental exosomes. Here we investigated whether placental exosomes in GDM carry a specific set of miRNAs associated with skeletal muscle insulin sensitivity. Exosomes were isolated from chorionic villous (CV) explants from both women with Normal Glucose Tolerant (NGT) and GDM pregnancies. Using miRNA sequencing, we identified a specific set of miRNAs selectively enriched with exosomes and compared with their cells of origin indicating a specific packaging of miRNAs into exosomes. Gene target and ontology analysis of miRNA differentially expressed in exosomes secreted in GDM compared with NGT are associated with pathways regulating cell migration and carbohydrate metabolism. We determined the expression of a selected set of miRNAs in placenta, plasma, and skeletal muscle biopsies from NGT and GDM. Interestingly, the expression of these miRNAs varied in a consistent pattern in the placenta, in circulating exosomes, and in skeletal muscle in GDM. Placental exosomes from GDM pregnancies decreased insulin-stimulated migration and glucose uptake in primary skeletal muscle cells obtained from patients with normal insulin sensitivity. Interestingly, placental exosomes from NGT increase migration and glucose uptake in response to insulin in skeletal muscle from diabetic subjects. These findings suggest that placental exosomes might have a role in the changes on insulin sensitivity in normal and GDM pregnancies.
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α-Smooth muscle actin staining of perinatal nicotine exposed bone marrow mesenchymal stem cells (BMSCs) upon myogenic induction. In Clinical Science volume 132, issue 21, Sakurai et al. report that perinatal nicotine-induced BMSC myofibroblast differentiation can be prevented by augmenting the lipofibroblast phenotype; for details, see pages 2357–2368.Close Modal
Research Article|
November 30 2018
Human placental exosomes in gestational diabetes mellitus carry a specific set of miRNAs associated with skeletal muscle insulin sensitivity
Soumyalekshmi Nair;
Soumyalekshmi Nair
1Exosome Biology Laboratory, Centre for Clinical Diagnostics, University of Queensland Centre for Clinical Research, Royal Brisbane and Women’s Hospital, The University of Queensland, Brisbane, QLD 4029, Australia
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Nanthini Jayabalan;
Nanthini Jayabalan
1Exosome Biology Laboratory, Centre for Clinical Diagnostics, University of Queensland Centre for Clinical Research, Royal Brisbane and Women’s Hospital, The University of Queensland, Brisbane, QLD 4029, Australia
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Dominic Guanzon;
Dominic Guanzon
1Exosome Biology Laboratory, Centre for Clinical Diagnostics, University of Queensland Centre for Clinical Research, Royal Brisbane and Women’s Hospital, The University of Queensland, Brisbane, QLD 4029, Australia
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Carlos Palma;
Carlos Palma
1Exosome Biology Laboratory, Centre for Clinical Diagnostics, University of Queensland Centre for Clinical Research, Royal Brisbane and Women’s Hospital, The University of Queensland, Brisbane, QLD 4029, Australia
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Katherin Scholz-Romero;
Katherin Scholz-Romero
1Exosome Biology Laboratory, Centre for Clinical Diagnostics, University of Queensland Centre for Clinical Research, Royal Brisbane and Women’s Hospital, The University of Queensland, Brisbane, QLD 4029, Australia
2Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepción, Concepción, Chile
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Omar Elfeky;
Omar Elfeky
1Exosome Biology Laboratory, Centre for Clinical Diagnostics, University of Queensland Centre for Clinical Research, Royal Brisbane and Women’s Hospital, The University of Queensland, Brisbane, QLD 4029, Australia
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Felipe Zuñiga;
Felipe Zuñiga
2Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepción, Concepción, Chile
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Valeska Ormazabal;
Valeska Ormazabal
3Department of Pharmacology, Faculty of Biological Sciences, University of Concepcion, Chile
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Emilio Diaz;
Emilio Diaz
4Faculty of Medicine, University of Concepcion, Concepcion, Chile
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Gregory E. Rice;
Gregory E. Rice
1Exosome Biology Laboratory, Centre for Clinical Diagnostics, University of Queensland Centre for Clinical Research, Royal Brisbane and Women’s Hospital, The University of Queensland, Brisbane, QLD 4029, Australia
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Gregory Duncombe;
Gregory Duncombe
1Exosome Biology Laboratory, Centre for Clinical Diagnostics, University of Queensland Centre for Clinical Research, Royal Brisbane and Women’s Hospital, The University of Queensland, Brisbane, QLD 4029, Australia
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Thomas Jansson;
Thomas Jansson
5Department of Obstetrics and Gynecology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, U.S.A.
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Harold David McIntyre;
Harold David McIntyre
6Mater Research, Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
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Martha Lappas;
Martha Lappas
7Obstetrics, Nutrition and Endocrinology Group, Department of Obstetrics and Gynaecology, University of Melbourne, Victoria, Australia; Mercy Perinatal Research Centre, Mercy Hospital for Women, Victoria, Australia
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Carlos Salomon
1Exosome Biology Laboratory, Centre for Clinical Diagnostics, University of Queensland Centre for Clinical Research, Royal Brisbane and Women’s Hospital, The University of Queensland, Brisbane, QLD 4029, Australia
2Department of Clinical Biochemistry and Immunology, Faculty of Pharmacy, University of Concepción, Concepción, Chile
Correspondence: Carlos Salomon (c.salomongallo@uq.edu.au)
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Clin Sci (Lond) (2018) 132 (22): 2451–2467.
Article history
Received:
June 11 2018
Revision Received:
September 10 2018
Accepted:
September 25 2018
Accepted Manuscript online:
September 25 2018
Citation
Soumyalekshmi Nair, Nanthini Jayabalan, Dominic Guanzon, Carlos Palma, Katherin Scholz-Romero, Omar Elfeky, Felipe Zuñiga, Valeska Ormazabal, Emilio Diaz, Gregory E. Rice, Gregory Duncombe, Thomas Jansson, Harold David McIntyre, Martha Lappas, Carlos Salomon; Human placental exosomes in gestational diabetes mellitus carry a specific set of miRNAs associated with skeletal muscle insulin sensitivity. Clin Sci (Lond) 30 November 2018; 132 (22): 2451–2467. doi: https://doi.org/10.1042/CS20180487
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