miR-409-3p is reduced in plasma and islet immune infiltrates of NOD diabetic mice and is differentially expressed in people with type 1 diabetes

Diabetologia. 2020 Jan;63(1):124-136. doi: 10.1007/s00125-019-05026-1. Epub 2019 Oct 28.


Aims/hypothesis: MicroRNAs (miRNAs) are a novel class of potential biomarkers emerging in many diseases, including type 1 diabetes. Here, we aim to analyse a panel of circulating miRNAs in non-obese diabetic (NOD) mice and individuals with type 1 diabetes.

Methods: We adopted standardised methodologies for extracting miRNAs from small sample volumes to evaluate a profiling panel of mature miRNAs in paired plasma and laser-captured microdissected immune-infiltrated islets of recently diabetic and normoglycaemic NOD mice. Moreover, we validated the findings during disease progression and remission after anti-CD3 therapy in NOD mice, as well as in individuals with type 1 diabetes.

Results: Plasma levels of five miRNAs were downregulated in diabetic vs normoglycaemic mice. Of those, miR-409-3p was also downregulated in situ in the immune islet infiltrates of diabetic mice, suggesting an association with disease pathogenesis. Target-prediction tools linked miR-409-3p to immune- and metabolism-related signalling molecules. In situ miR-409-3p expression correlated with insulitis severity, and CD8+ central memory T cells were found to be enriched in miR-409-3p. Plasma miR-409-3p levels gradually decreased during diabetes development and improved with disease remission after anti-CD3 antibody therapy. Finally, plasma miR-409-3p levels were lower in people recently diagnosed with type 1 diabetes compared with a non-diabetic control group, and levels were inversely correlated with HbA1c levels.

Conclusions/interpretation: We propose that miR-409-3p may represent a new circulating biomarker of islet inflammation and type 1 diabetes severity.

Keywords: Anti-CD3 therapy; Biomarker; Inflammation; MicroRNA; Progression; Type 1 diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Diabetes Mellitus, Type 1 / genetics*
  • Female
  • Flow Cytometry
  • Gene Expression Profiling
  • Humans
  • Mice
  • Mice, Inbred NOD / genetics*
  • MicroRNAs / genetics*
  • Real-Time Polymerase Chain Reaction


  • Biomarkers
  • MIRN409 microRNA, mouse
  • MicroRNAs