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Diabetologia
Published in: Diabetologia 8/2015

01-08-2015 | Article

Involvement of long non-coding RNAs in beta cell failure at the onset of type 1 diabetes in NOD mice

Authors: Anna Motterle, Sonia Gattesco, Dorothée Caille, Paolo Meda, Romano Regazzi

Published in: Diabetologia | Issue 8/2015

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Abstract

Aims/hypothesis

Exposure of pancreatic beta cells to cytokines released by islet-infiltrating immune cells induces alterations in gene expression, leading to impaired insulin secretion and apoptosis in the initial phases of type 1 diabetes. Long non-coding RNAs (lncRNAs) are a new class of transcripts participating in the development of many diseases. As little is known about their role in insulin-secreting cells, this study aimed to evaluate their contribution to beta cell dysfunction.

Methods

The expression of lncRNAs was determined by microarray in the MIN6 beta cell line exposed to proinflammatory cytokines. The changes induced by cytokines were further assessed by real-time PCR in islets of control and NOD mice. The involvement of selected lncRNAs modified by cytokines was assessed after their overexpression in MIN6 cells and primary islet cells.

Results

MIN6 cells were found to express a large number of lncRNAs, many of which were modified by cytokine treatment. The changes in the level of selected lncRNAs were confirmed in mouse islets and an increase in these lncRNAs was also seen in prediabetic NOD mice. Overexpression of these lncRNAs in MIN6 and mouse islet cells, either alone or in combination with cytokines, favoured beta cell apoptosis without affecting insulin production or secretion. Furthermore, overexpression of lncRNA-1 promoted nuclear translocation of nuclear factor of κ light polypeptide gene enhancer in B cells 1 (NF-κB).

Conclusions/interpretation

Our study shows that lncRNAs are modulated during the development of type 1 diabetes in NOD mice, and that their overexpression sensitises beta cells to apoptosis, probably contributing to their failure during the initial phases of the disease.
Appendix
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Metadata
Title
Involvement of long non-coding RNAs in beta cell failure at the onset of type 1 diabetes in NOD mice
Authors
Anna Motterle
Sonia Gattesco
Dorothée Caille
Paolo Meda
Romano Regazzi
Publication date
01-08-2015
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 8/2015
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-015-3641-5

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