Human placental exosomes in gestational diabetes mellitus carry a specific set of miRNAs associated with skeletal muscle insulin sensitivity
| Autor: | Soumyalekshmi Nair, Felipe Zuñiga, Dominic Guanzon, Carlos Salomon, Gregory Duncombe, Katherin Scholz-Romero, Omar Elfeky, Thomas Jansson, Gregory E. Rice, Harold David McIntyre, Valeska Ormazabal, Emilio Diaz, Nanthini Jayabalan, Martha Lappas, Carlos Palma |
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| Rok vydání: | 2018 |
| Předmět: |
Adult
0301 basic medicine medicine.medical_specialty endocrine system diseases Myoblasts Skeletal medicine.medical_treatment Biology Exosomes Young Adult 03 medical and health sciences Insulin resistance Cell Movement Pregnancy Placenta Internal medicine Diabetes mellitus medicine Humans Hypoglycemic Agents Insulin Myocyte Cells Cultured nutritional and metabolic diseases Skeletal muscle General Medicine medicine.disease Microvesicles Gestational diabetes Diabetes Gestational MicroRNAs Glucose 030104 developmental biology medicine.anatomical_structure Endocrinology Case-Control Studies Female Chorionic Villi Insulin Resistance Transcriptome |
| Zdroj: | Clinical Science. 132:2451-2467 |
| ISSN: | 1470-8736 0143-5221 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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