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ludc web

Lena Eliasson

Principal investigator

ludc web

PIWI-interacting RNAs as novel regulators of pancreatic beta cell function

Author

  • Imène Sarah Henaoui
  • Cécile Jacovetti
  • Ines Mollet
  • Claudiane Guay
  • Jonathan Sobel
  • Lena Eliasson
  • Romano Regazzi

Summary, in English

Aims/hypothesis: P-element induced Wimpy testis (PIWI)-interacting RNAs (piRNAs) are small non-coding RNAs that interact with PIWI proteins and guide them to silence transposable elements. They are abundantly expressed in germline cells and play key roles in spermatogenesis. There is mounting evidence that piRNAs are also present in somatic cells, where they may accomplish additional regulatory tasks. The aim of this study was to identify the piRNAs expressed in pancreatic islets and to determine whether they are involved in the control of beta cell activities. Methods: piRNA profiling of rat pancreatic islets was performed by microarray analysis. The functions of piRNAs were investigated by silencing the two main Piwi genes or by modulating the level of selected piRNAs in islet cells. Results: We detected about 18,000 piRNAs in rat pancreatic islets, many of which were differentially expressed throughout islet postnatal development. Moreover, we identified changes in the level of several piRNAs in the islets of Goto–Kakizaki rats, a well-established animal model of type 2 diabetes. Silencing of Piwil2 or Piwil4 genes in adult rat islets caused a reduction in the level of several piRNAs and resulted in defective insulin secretion and increased resistance of the cells to cytokine-induced cell death. Furthermore, overexpression in the islets of control animals of two piRNAs that are upregulated in diabetic rats led to a selective defect in glucose-induced insulin release. Conclusions/interpretation: Our results provide evidence for a role of PIWI proteins and their associated piRNAs in the control of beta cell functions, and suggest a possible involvement in the development of type 2 diabetes. Data availability: Data have been deposited in Gene Expression Omnibus repository under the accession number GSE93792. Data can be accessed via the following link: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?token=ojklueugdzehpkv&ac…

Department/s

  • Diabetes - Islet Cell Exocytosis
  • Cardiovascular Research - Immunity and Atherosclerosis
  • EXODIAB: Excellence of Diabetes Research in Sweden

Publishing year

2017-07-16

Language

English

Pages

1977-1986

Publication/Series

Diabetologia

Volume

60

Issue

10

Document type

Journal article

Publisher

Springer

Topic

  • Endocrinology and Diabetes

Keywords

  • Diabetes
  • Insulin secretion
  • Pancreatic islets
  • piRNAs
  • Piwil genes

Status

Published

Research group

  • Diabetes - Islet Cell Exocytosis
  • Cardiovascular Research - Immunity and Atherosclerosis

ISBN/ISSN/Other

  • ISSN: 0012-186X