期刊
ENDOCRINOLOGY
卷 154, 期 2, 页码 603-608出版社
ENDOCRINE SOC
DOI: 10.1210/en.2012-1744
关键词
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资金
- Juvenile Diabetes Research Foundation (JDRF)
- Michael Smith Foundation for Health Research (MSFHR)
- Swiss National Science Foundation
- Canadian Institutes for Health Research Transplantation Training Program
- Natural Sciences and Engineering Research Council of Canada
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 studywesought to determine whetheranislet enrichedmiRNA, 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. (Endocrinology 154: 603-608, 2013)
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