Academic Journal
miR-375 gene dosage in pancreatic β-cells: implications for regulation of β-cell mass and biomarker development
| العنوان: | miR-375 gene dosage in pancreatic β-cells: implications for regulation of β-cell mass and biomarker development |
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| المؤلفون: | Latreille, M, Herrmanns, K, Renwick, N, Tuschl, T, Malecki, MT, McCarthy, MI, Owen, KR, Rülicke, T, Stoffel, M |
| المصدر: | 1169 ; 1159 |
| بيانات النشر: | Springer Verlag |
| سنة النشر: | 2015 |
| المجموعة: | Imperial College London: Spiral |
| مصطلحات موضوعية: | Immunology, 0304 Medicinal And Biomolecular Chemistry |
| الوصف: | MicroRNAs play a crucial role in the regulation of cell growth and differentiation. Mice with genetic deletion of miR-375 exhibit impaired glycemic control due to decreased β-cell and increased α-cell mass and function. The relative importance of these processes for the overall phenotype of miR-375KO mice is unknown. Here, we show that mice overexpressing miR-375 exhibit normal β-cell mass and function. Selective re-expression of miR-375 in β-cells of miR-375KO mice normalizes both, α- and β-cell phenotypes as well as glucose metabolism. Using this model, we also analyzed the contribution of β-cells to the total plasma miR-375 levels. Only a small proportion (≈1 %) of circulating miR-375 originates from β-cells. Furthermore, acute and profound β-cell destruction is sufficient to detect elevations of miR-375 levels in the blood. These findings are supported by higher miR-375 levels in the circulation of type 1 diabetes (T1D) subjects but not mature onset diabetes of the young (MODY) and type 2 diabetes (T2D) patients. Together, our data support an essential role for miR-375 in the maintenance of β-cell mass and provide in vivo evidence for release of miRNAs from pancreatic β-cells. The small contribution of β-cells to total plasma miR-375 levels make this miRNA an unlikely biomarker for β-cell function but suggests a utility for the detection of acute β-cell death for autoimmune diabetes. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| تدمد: | 1432-1440 |
| Relation: | Journal of Molecular Medicine-JMM; http://hdl.handle.net/10044/1/44026; http://dx.doi.org/10.1007/s00109-015-1296-9 |
| DOI: | 10.1007/s00109-015-1296-9 |
| الاتاحة: | http://hdl.handle.net/10044/1/44026 https://doi.org/10.1007/s00109-015-1296-9 |
| Rights: | © 2015 The Authors. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. |
| رقم الانضمام: | edsbas.B827B056 |
| قاعدة البيانات: | BASE |
| تدمد: | 14321440 |
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| DOI: | 10.1007/s00109-015-1296-9 |