title: Involvement of long non-coding RNAs in beta cell failure at the onset of type 1 diabetes in NOD mice.
abstract: OBJECTIVE
  Exposure of pancreatic beta cells to cytokines released by islet-infiltrating immune cells induces alterations in gene expression, leading to impaired insulin secretion and apoptosis in the initial phases of type 1 diabetes. Long non-coding RNAs (lncRNAs) are a new class of transcripts participating in the development of many diseases. As little is known about their role in insulin-secreting cells, this study aimed to evaluate their contribution to beta cell dysfunction.
  
  
  METHODS
  The expression of lncRNAs was determined by microarray in the MIN6 beta cell line exposed to proinflammatory cytokines. The changes induced by cytokines were further assessed by real-time PCR in islets of control and NOD mice. The involvement of selected lncRNAs modified by cytokines was assessed after their overexpression in MIN6 cells and primary islet cells.
  
  
  RESULTS
  MIN6 cells were found to express a large number of lncRNAs, many of which were modified by cytokine treatment. The changes in the level of selected lncRNAs were confirmed in mouse islets and an increase in these lncRNAs was also seen in prediabetic NOD mice. Overexpression of these lncRNAs in MIN6 and mouse islet cells, either alone or in combination with cytokines, favoured beta cell apoptosis without affecting insulin production or secretion. Furthermore, overexpression of lncRNA-1 promoted nuclear translocation of nuclear factor of κ light polypeptide gene enhancer in B cells 1 (NF-κB).
  
  
  CONCLUSIONS
  Our study shows that lncRNAs are modulated during the development of type 1 diabetes in NOD mice, and that their overexpression sensitises beta cells to apoptosis, probably contributing to their failure during the initial phases of the disease.
authors.affiliation: Department of Fundamental Neurosciences, Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 9, 1005, Lausanne, Switzerland.
authors.forename: Anna
authors.initials: A
authors.lastname: Motterle
authors.forename: Sonia
authors.initials: S
authors.lastname: Gattesco
authors.forename: Dorothée
authors.initials: D
authors.lastname: Caille
authors.forename: Paolo
authors.initials: P
authors.lastname: Meda
authors.forename: Romano
authors.initials: R
authors.lastname: Regazzi
mesh_terms: D000818:Animals; D002460:Cell Line; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000473:pathology; D018450:Disease Progression; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D007515:Islets of Langerhans / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D016688:Mice, Inbred NOD; D011236:Prediabetic State / Q000378:metabolism* / Q000473:pathology; D062085:RNA, Long Noncoding
chemical_list: D007328:Insulin; D062085:RNA, Long Noncoding