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Identification of i...
Identification of islet-enriched long non-coding RNAs contributing to β-cell failure in type 2 diabetes
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- Motterle, Anna (author)
- University of Lausanne
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- Gattesco, Sonia (author)
- University of Lausanne
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- Peyot, Marie Line (author)
- Montreal Diabetes Research Centre (MDRC)
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- Esguerra, Jonathan Lou S. (author)
- Lund University,Lunds universitet,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Diabetes - Islet Cell Exocytosis,Lund University Research Groups
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- Ruiz-Gomez, Ana (author)
- Catholic University of Louvain
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- Laybutt, D Ross (author)
- St Vincent's Hospital, Sydney,University of New South Wales
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- Gilon, Patrick (author)
- Catholic University of Louvain
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- Burdet, Frédéric (author)
- Swiss Institute for Bioinformatics (SIB)
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- Ibberson, Mark (author)
- Swiss Institute for Bioinformatics (SIB)
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- Eliasson, Lena (author)
- Lund University,Lunds universitet,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Diabetes - Islet Cell Exocytosis,Lund University Research Groups
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- Prentki, Marc (author)
- Montreal Diabetes Research Centre (MDRC)
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- Regazzi, Romano (author)
- University of Lausanne
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(creator_code:org_t)
- Elsevier BV, 2017
- 2017
- English.
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In: Molecular Metabolism. - : Elsevier BV. - 2212-8778. ; 6:11, s. 1407-1418
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Abstract
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- Objective: 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. Methods: 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. Results: 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. Conclusions: 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Keyword
- Diabetes
- Gene expression
- Insulin
- Obesity
- Pancreatic islet
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Motterle, Anna
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Gattesco, Sonia
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Peyot, Marie Lin ...
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Esguerra, Jonath ...
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Ruiz-Gomez, Ana
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Laybutt, D Ross
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show more...
-
Gilon, Patrick
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Burdet, Frédéric
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Ibberson, Mark
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Eliasson, Lena
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Prentki, Marc
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Regazzi, Romano
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Endocrinology an ...
- Articles in the publication
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Molecular Metabo ...
- By the university
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Lund University