Identification of islet-enriched long non-coding RNAs contributing to β-cell failure in type 2 diabetes
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...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-11-01
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| Series: | Molecular Metabolism |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877817305409 |
| _version_ | 1818572797127950336 |
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| author | Anna Motterle Sonia Gattesco Marie-Line Peyot Jonathan Lou S. Esguerra Ana Gomez-Ruiz D. Ross Laybutt Patrick Gilon Frédéric Burdet Mark Ibberson Lena Eliasson Marc Prentki Romano Regazzi |
| author_facet | Anna Motterle Sonia Gattesco Marie-Line Peyot Jonathan Lou S. Esguerra Ana Gomez-Ruiz D. Ross Laybutt Patrick Gilon Frédéric Burdet Mark Ibberson Lena Eliasson Marc Prentki Romano Regazzi |
| author_sort | Anna Motterle |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-15T00:02:27Z |
| format | Article |
| id | doaj.art-3b8e45242e6146db91dafa93326fa629 |
| institution | Directory Open Access Journal |
| issn | 2212-8778 |
| language | English |
| last_indexed | 2024-12-15T00:02:27Z |
| publishDate | 2017-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Metabolism |
| spelling | doaj.art-3b8e45242e6146db91dafa93326fa6292022-12-21T22:42:51ZengElsevierMolecular Metabolism2212-87782017-11-016111407141810.1016/j.molmet.2017.08.005Identification of islet-enriched long non-coding RNAs contributing to β-cell failure in type 2 diabetesAnna Motterle0Sonia Gattesco1Marie-Line Peyot2Jonathan Lou S. Esguerra3Ana Gomez-Ruiz4D. Ross Laybutt5Patrick Gilon6Frédéric Burdet7Mark Ibberson8Lena Eliasson9Marc Prentki10Romano Regazzi11Department of Fundamental Neurosciences, Faculty of Biology and Medicine, University of Lausanne, SwitzerlandDepartment of Fundamental Neurosciences, Faculty of Biology and Medicine, University of Lausanne, SwitzerlandMontreal Diabetes Research Center and Centre de Recherche du CHUM, Montréal, Québec, CanadaDepartment of Clinical Sciences-Malmö, Lund University Diabetes Centre, Lund University, Clinical Research Centre, SUS, Malmö, SwedenPôle d'Endocrinologie, Diabète et Nutrition, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, BelgiumGarvan Institute of Medical Research, St Vincent's Hospital, University of New South Wales, Sydney AustraliaPôle d'Endocrinologie, Diabète et Nutrition, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, BelgiumVital-IT group, Swiss Institute of Bioinformatics, Lausanne, SwitzerlandVital-IT group, Swiss Institute of Bioinformatics, Lausanne, SwitzerlandDepartment of Clinical Sciences-Malmö, Lund University Diabetes Centre, Lund University, Clinical Research Centre, SUS, Malmö, SwedenMontreal Diabetes Research Center and Centre de Recherche du CHUM, Montréal, Québec, CanadaDepartment of Fundamental Neurosciences, Faculty of Biology and Medicine, University of Lausanne, SwitzerlandObjective: 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.http://www.sciencedirect.com/science/article/pii/S2212877817305409DiabetesInsulinPancreatic isletObesityGene expression |
| spellingShingle | Anna Motterle Sonia Gattesco Marie-Line Peyot Jonathan Lou S. Esguerra Ana Gomez-Ruiz D. Ross Laybutt Patrick Gilon Frédéric Burdet Mark Ibberson Lena Eliasson Marc Prentki Romano Regazzi Identification of islet-enriched long non-coding RNAs contributing to β-cell failure in type 2 diabetes Molecular Metabolism Diabetes Insulin Pancreatic islet Obesity Gene expression |
| title | Identification of islet-enriched long non-coding RNAs contributing to β-cell failure in type 2 diabetes |
| title_full | Identification of islet-enriched long non-coding RNAs contributing to β-cell failure in type 2 diabetes |
| title_fullStr | Identification of islet-enriched long non-coding RNAs contributing to β-cell failure in type 2 diabetes |
| title_full_unstemmed | Identification of islet-enriched long non-coding RNAs contributing to β-cell failure in type 2 diabetes |
| title_short | Identification of islet-enriched long non-coding RNAs contributing to β-cell failure in type 2 diabetes |
| title_sort | identification of islet enriched long non coding rnas contributing to β cell failure in type 2 diabetes |
| topic | Diabetes Insulin Pancreatic islet Obesity Gene expression |
| url | http://www.sciencedirect.com/science/article/pii/S2212877817305409 |
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