| First Author | Motterle A | Year | 2017 |
| Journal | Mol Metab | Volume | 6 |
| Issue | 11 | Pages | 1407-1418 |
| PubMed ID | 29107288 | Mgi Jnum | J:270366 |
| Mgi Id | MGI:6161908 | Doi | 10.1016/j.molmet.2017.08.005 |
| Citation | Motterle A, et al. (2017) Identification of islet-enriched long non-coding RNAs contributing to beta-cell failure in type 2 diabetes. Mol Metab 6(11):1407-1418 |
| abstractText | OBJECTIVE: Non-coding RNAs constitute a major fraction of the beta-cell transcriptome. While the involvement of microRNAs is well established, the contribution of long non-coding RNAs (lncRNAs) in the regulation of beta-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 beta-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 beta-cells, betalinc2, and betalinc3, 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 betalinc3 was altered in the islets of type 2 diabetic patients and was associated to the BMI of the donors. Modulation of the level of betalinc2 and betalinc3 by overexpression or downregulation in MIN6 and mouse islet cells did not affect insulin secretion but increased beta-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 beta-cell failure during the development of the disease. |
