Identification of islet-enriched long non-coding RNAs contributing to β-cell failure in type 2 diabetes.

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State: Public
Version: Final published version
Serval ID
serval:BIB_D238F81A7442
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Identification of islet-enriched long non-coding RNAs contributing to β-cell failure in type 2 diabetes.
Journal
Molecular metabolism
Author(s)
Motterle A., Gattesco S., Peyot M.L., Esguerra JLS, Gomez-Ruiz A., Laybutt D.R., Gilon P., Burdet F., Ibberson M., Eliasson L., Prentki M., Regazzi R.
ISSN
2212-8778 (Electronic)
ISSN-L
2212-8778
Publication state
Published
Issued date
11/2017
Peer-reviewed
Oui
Volume
6
Number
11
Pages
1407-1418
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Non-coding RNAs constitute a major fraction of the β-cell transcriptome. While the involvement of microRNAs is well established, the contribution of long non-coding RNAs (lncRNAs) in the regulation of β-cell functions and in diabetes development remains poorly understood. The aim of this study was to identify novel islet lncRNAs differently expressed in type 2 diabetes models and to investigate their role in β-cell failure and in the development of the disease.
Novel transcripts dysregulated in the islets of diet-induced obese mice were identified by high throughput RNA-sequencing coupled with de novo annotation. Changes in the level of the lncRNAs were assessed by real-time PCR. The functional role of the selected lncRNAs was determined by modifying their expression in MIN6 cells and primary islet cells.
We identified about 1500 novel lncRNAs, a number of which were differentially expressed in obese mice. The expression of two lncRNAs highly enriched in β-cells, βlinc2, and βlinc3, correlated to body weight gain and glycemia levels in obese mice and was also modified in diabetic db/db mice. The expression of both lncRNAs was also modulated in vitro in isolated islet cells by glucolipotoxic conditions. Moreover, the expression of the human orthologue of βlinc3 was altered in the islets of type 2 diabetic patients and was associated to the BMI of the donors. Modulation of the level of βlinc2 and βlinc3 by overexpression or downregulation in MIN6 and mouse islet cells did not affect insulin secretion but increased β-cell apoptosis.
Taken together, the data show that lncRNAs are modulated in a model of obesity-associated type 2 diabetes and that variations in the expression of some of them may contribute to β-cell failure during the development of the disease.
Keywords
Animals, Diabetes Mellitus, Type 2/genetics, Diabetes Mellitus, Type 2/metabolism, Diet, High-Fat, Disease Models, Animal, Gene Expression/genetics, Insulin/metabolism, Insulin-Secreting Cells/metabolism, Islets of Langerhans/metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Obese, RNA, Long Noncoding/genetics, RNA, Long Noncoding/metabolism, Sequence Analysis, RNA, Transcriptome, Diabetes, Gene expression, Insulin, Obesity, Pancreatic islet
Pubmed
Web of science
Open Access
Yes
Create date
15/11/2017 9:57
Last modification date
20/08/2019 15:52
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