GSE92602

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Summary

To study the contribution of long non-coding RNAs (lncRNAs) to beta-cell failure and the development of type 2 diabetes, we used RNA-sequencing coupled with de novo annotation to search for novel transcripts dysregulated in islets of diet-induced obese mice. 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, βlinc2 and βlinc3, correlated to body weight gain and glycaemia 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 islets 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 islets cells, did not affect insulin secretion but increased beta-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 beta-cell failure during the development of the disease.