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

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.

Author information

1
Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, V.le Bracci, 16 - 53100, Siena, Italy.
2
Fondazione Umberto Di Mario ONLUS c/o Toscana Life Sciences, Siena, Italy.
3
Clinical and Experimental Endocrinology (CEE), Katholieke Universiteit Leuven (KU LEUVEN), Leuven, Belgium.
4
Inserm, U1016, CNRS, UMR8104, Paris Descartes University, Sorbonne Paris Cité, Cochin Institute, Paris, France.
5
Diabetes Unit, Department of Medicine, Surgery and Neurosciences, University of Siena, V.le Bracci, 16 - 53100, Siena, Italy. francesco.dotta@unisi.it.
6
Fondazione Umberto Di Mario ONLUS c/o Toscana Life Sciences, Siena, Italy. francesco.dotta@unisi.it.

Abstract

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

PMID:
31659408
DOI:
10.1007/s00125-019-05026-1

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