title: Circulating miR-375 as a biomarker of β-cell death and diabetes in mice.
abstract: Type 1 diabetes is a progressive autoimmune disease that is largely silent in its initial stages. Yet, sensitive methods for detection of β-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 β-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 β-cell death and potential predictor of diabetes.
authors: Department of Cellular and Physiological Sciences, 2350 Health Science Mall, University of British Columbia, V6T 1Z3 Vancouver, British Columbia, Canada.
authors: Suheda
authors: S
authors: Erener
authors: Majid
authors: M
authors: Mojibian
authors: Jessica K
authors: JK
authors: Fox
authors: Heather C
authors: HC
authors: Denroche
authors: Timothy J
authors: TJ
authors: Kieffer
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D005260:Female; D006801:Humans; D050417:Insulin-Secreting Cells / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D035683:MicroRNAs / Q000097:blood*; D013311:Streptozocin
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; C540349:Mirn375 microRNA, mouse; D013311:Streptozocin