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. |