miRNA-375 a Sensor of Glucotoxicity Is Altered in the Serum of Children with Newly Diagnosed Type 1 Diabetes
Background. The use of miRNAs as biomarkers for Type 1 Diabetes (T1D) risk is attractive as T1D is usually diagnosed in front of acute symptoms. As miR-375 is highly expressed in the endocrine pancreas, we postulated that its circulating level might reflect beta cell alterations and might be altered...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2016/1869082 |
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| author | Lucien Marchand Audrey Jalabert Emmanuelle Meugnier Kathleen Van den Hende Nicole Fabien Marc Nicolino Anne-Marie Madec Charles Thivolet Sophie Rome |
| author_facet | Lucien Marchand Audrey Jalabert Emmanuelle Meugnier Kathleen Van den Hende Nicole Fabien Marc Nicolino Anne-Marie Madec Charles Thivolet Sophie Rome |
| author_sort | Lucien Marchand |
| collection | DOAJ |
| description | Background. The use of miRNAs as biomarkers for Type 1 Diabetes (T1D) risk is attractive as T1D is usually diagnosed in front of acute symptoms. As miR-375 is highly expressed in the endocrine pancreas, we postulated that its circulating level might reflect beta cell alterations and might be altered in the blood of T1D patients recently diagnosed. Methods. Sera were obtained from 22 T1D children at onset of the disease, before subcutaneous insulin treatment, and from 10 nondiabetic pediatric controls. MiR-375 seric level was quantified by stem-loop RT-PCR-based assay. MiRNAs regulations in isolated human islets in response to high glucose concentrations were determined by TaqMan Low-Density Array. Results. The abundance of miR-375, among the 410 miRNAs detected in human islets, mirrored its well-established role in rodent islet biology. Upregulated miRNAs targeted genes involved in islet homeostasis and regulation of beta cell mass. Downregulated miRNAs, including miR-375, were involved in pancreas secretion and protein turnover. Seric level of miR-375 was lower in T1D children versus age-matched controls, without any correlations with HbA1c, glycaemia, and number of autoantibodies. Conclusion. Altered circulating level of miR-375 at onset of T1D might be a general biomarker of metabolic alterations and inflammation associated with the disease. |
| format | Article |
| id | doaj-art-9a0fcb43c2de4a4ea1504f2990e02b47 |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-9a0fcb43c2de4a4ea1504f2990e02b472025-02-03T07:26:00ZengWileyJournal of Diabetes Research2314-67452314-67532016-01-01201610.1155/2016/18690821869082miRNA-375 a Sensor of Glucotoxicity Is Altered in the Serum of Children with Newly Diagnosed Type 1 DiabetesLucien Marchand0Audrey Jalabert1Emmanuelle Meugnier2Kathleen Van den Hende3Nicole Fabien4Marc Nicolino5Anne-Marie Madec6Charles Thivolet7Sophie Rome8CarMeN Laboratory (INSERM 1060, INRA 1362, INSA), Lyon-Sud Faculty of Medicine, University of Lyon, Chemin du Grand Revoyet, 69600 Oullins, FranceCarMeN Laboratory (INSERM 1060, INRA 1362, INSA), Lyon-Sud Faculty of Medicine, University of Lyon, Chemin du Grand Revoyet, 69600 Oullins, FranceCarMeN Laboratory (INSERM 1060, INRA 1362, INSA), Lyon-Sud Faculty of Medicine, University of Lyon, Chemin du Grand Revoyet, 69600 Oullins, FranceHospices Civils de Lyon, Department of Pediatric Endocrinology, Femme-Mère-Enfant Hospital, 69500 Bron, FranceHospices Civils de Lyon, INSERM U851, Lyon-Sud Hospital, Department of Immunology, 69495 Pierre-Bénite, FranceCarMeN Laboratory (INSERM 1060, INRA 1362, INSA), Lyon-Sud Faculty of Medicine, University of Lyon, Chemin du Grand Revoyet, 69600 Oullins, FranceCarMeN Laboratory (INSERM 1060, INRA 1362, INSA), Lyon-Sud Faculty of Medicine, University of Lyon, Chemin du Grand Revoyet, 69600 Oullins, FranceCarMeN Laboratory (INSERM 1060, INRA 1362, INSA), Lyon-Sud Faculty of Medicine, University of Lyon, Chemin du Grand Revoyet, 69600 Oullins, FranceCarMeN Laboratory (INSERM 1060, INRA 1362, INSA), Lyon-Sud Faculty of Medicine, University of Lyon, Chemin du Grand Revoyet, 69600 Oullins, FranceBackground. The use of miRNAs as biomarkers for Type 1 Diabetes (T1D) risk is attractive as T1D is usually diagnosed in front of acute symptoms. As miR-375 is highly expressed in the endocrine pancreas, we postulated that its circulating level might reflect beta cell alterations and might be altered in the blood of T1D patients recently diagnosed. Methods. Sera were obtained from 22 T1D children at onset of the disease, before subcutaneous insulin treatment, and from 10 nondiabetic pediatric controls. MiR-375 seric level was quantified by stem-loop RT-PCR-based assay. MiRNAs regulations in isolated human islets in response to high glucose concentrations were determined by TaqMan Low-Density Array. Results. The abundance of miR-375, among the 410 miRNAs detected in human islets, mirrored its well-established role in rodent islet biology. Upregulated miRNAs targeted genes involved in islet homeostasis and regulation of beta cell mass. Downregulated miRNAs, including miR-375, were involved in pancreas secretion and protein turnover. Seric level of miR-375 was lower in T1D children versus age-matched controls, without any correlations with HbA1c, glycaemia, and number of autoantibodies. Conclusion. Altered circulating level of miR-375 at onset of T1D might be a general biomarker of metabolic alterations and inflammation associated with the disease.http://dx.doi.org/10.1155/2016/1869082 |
| spellingShingle | Lucien Marchand Audrey Jalabert Emmanuelle Meugnier Kathleen Van den Hende Nicole Fabien Marc Nicolino Anne-Marie Madec Charles Thivolet Sophie Rome miRNA-375 a Sensor of Glucotoxicity Is Altered in the Serum of Children with Newly Diagnosed Type 1 Diabetes Journal of Diabetes Research |
| title | miRNA-375 a Sensor of Glucotoxicity Is Altered in the Serum of Children with Newly Diagnosed Type 1 Diabetes |
| title_full | miRNA-375 a Sensor of Glucotoxicity Is Altered in the Serum of Children with Newly Diagnosed Type 1 Diabetes |
| title_fullStr | miRNA-375 a Sensor of Glucotoxicity Is Altered in the Serum of Children with Newly Diagnosed Type 1 Diabetes |
| title_full_unstemmed | miRNA-375 a Sensor of Glucotoxicity Is Altered in the Serum of Children with Newly Diagnosed Type 1 Diabetes |
| title_short | miRNA-375 a Sensor of Glucotoxicity Is Altered in the Serum of Children with Newly Diagnosed Type 1 Diabetes |
| title_sort | mirna 375 a sensor of glucotoxicity is altered in the serum of children with newly diagnosed type 1 diabetes |
| url | http://dx.doi.org/10.1155/2016/1869082 |
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