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

Henaoui, Imène Sarah; Jacovetti, Cécile; Mollet, Ines LU ; Guay, Claudiane; Sobel, Jonathan; Eliasson, Lena LU and Regazzi, Romano (2017) In Diabetologia 60(10). p.1977-1986
Abstract

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... (More)

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&acc=GSE93792

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Diabetes, Insulin secretion, Pancreatic islets, piRNAs, Piwil genes
in
Diabetologia
volume
60
issue
10
pages
1977 - 1986
publisher
Springer Verlag
external identifiers
  • scopus:85023781016
  • wos:000408770300015
ISSN
0012-186X
DOI
10.1007/s00125-017-4368-2
language
English
LU publication?
yes
id
03783d0e-090e-40ad-a54b-d870c49c43c7
date added to LUP
2017-08-02 10:38:39
date last changed
2018-01-16 13:22:13
@article{03783d0e-090e-40ad-a54b-d870c49c43c7,
  abstract     = {<p>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&amp;acc=GSE93792</p>},
  author       = {Henaoui, Imène Sarah and Jacovetti, Cécile and Mollet, Ines and Guay, Claudiane and Sobel, Jonathan and Eliasson, Lena and Regazzi, Romano},
  issn         = {0012-186X},
  keyword      = {Diabetes,Insulin secretion,Pancreatic islets,piRNAs,Piwil genes},
  language     = {eng},
  month        = {07},
  number       = {10},
  pages        = {1977--1986},
  publisher    = {Springer Verlag},
  series       = {Diabetologia},
  title        = {PIWI-interacting RNAs as novel regulators of pancreatic beta cell function},
  url          = {http://dx.doi.org/10.1007/s00125-017-4368-2},
  volume       = {60},
  year         = {2017},
}