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Publication : Circulating miR-375 as a biomarker of β-cell death and diabetes in mice.

First Author  Erener S Year  2013
Journal  Endocrinology Volume  154
Issue  2 Pages  603-8
PubMed ID  23321698 Mgi Jnum  J:195885
Mgi Id  MGI:5486101 Doi  10.1210/en.2012-1744
Citation  Erener S, et al. (2013) Circulating miR-375 as a biomarker of beta-cell death and diabetes in mice. Endocrinology 154(2):603-8
abstractText  Type 1 diabetes is a progressive autoimmune disease that is largely silent in its initial stages. Yet, sensitive methods for detection of beta-cell death and prediction and prevention of diabetes are lacking. Micro-RNAs (miRNAs) have been found at high concentrations in body fluids. Here in this study we sought to determine whether an islet enriched miRNA, miR-375, is a suitable blood marker to detect beta-cell death and predict diabetes in mice. We measured miR-375 levels by quantitative RT-PCR in plasma samples of streptozotocin (STZ)-treated C57BL/6 mice and nonobese diabetic (NOD) mice. We also measured miR-375 levels in media samples of cytokine- or STZ-treated islets in the presence or absence of cell-death inhibitors. High-dose STZ administration dramatically increased circulating miR-375 levels, prior to the onset of hyperglycemia. Similarly, in the NOD mouse model of autoimmune diabetes, circulating miR-375 levels were significantly increased 2 weeks before diabetes onset. Moreover, cytokine- and STZ-induced cell death in isolated mouse islets produced a striking increase in extracellular miR-375 levels, which was reduced by cell death inhibitors. These data suggest that circulating miR-375 can be used as a marker of beta-cell death and potential predictor of diabetes.
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