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

Endocrinology. 2013 Feb;154(2):603-8. doi: 10.1210/en.2012-1744. Epub 2013 Jan 15.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / blood*
  • Diabetes Mellitus, Experimental / metabolism*
  • Diabetes Mellitus, Type 1 / blood*
  • Female
  • Humans
  • Insulin-Secreting Cells / pathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred NOD
  • MicroRNAs / blood*
  • Streptozocin

Substances

  • Biomarkers
  • MicroRNAs
  • Mirn375 microRNA, mouse
  • Streptozocin