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In Vivo Silencing of MicroRNA-132 Reduces Blood Glucose and Improves Insulin Secretion

Bijkerk, Roel ; Esguerra, Jonathan L S LU orcid ; Ellenbroek, Johanne H ; Au, Yu Wah ; Hanegraaf, Maaike A J ; de Koning, Eelco J ; Eliasson, Lena LU orcid and van Zonneveld, Anton Jan (2019) In Nucleic acid therapeutics 29(2). p.67-72
Abstract

Dysfunctional insulin secretion is a hallmark of type 2 diabetes (T2D). Interestingly, several islet microRNAs (miRNAs) are upregulated in T2D, including miR-132. We aimed to investigate whether in vivo treatment with antagomir-132 lowers expression of miR-132 in islets thereby improving insulin secretion and lowering blood glucose. Mice injected with antagomir-132 for 24 h, had reduced expression of miR-132 expression in islets, decreased blood glucose, and increased insulin secretion. In isolated human islets treated with antagomir-132, insulin secretion from four of six donors increased. Target prediction coupled with analysis of miRNA-messenger RNA expression in human islets revealed DESI2, ARIH1, SLC25A28, DIAPH1, and FOXA1 to be... (More)

Dysfunctional insulin secretion is a hallmark of type 2 diabetes (T2D). Interestingly, several islet microRNAs (miRNAs) are upregulated in T2D, including miR-132. We aimed to investigate whether in vivo treatment with antagomir-132 lowers expression of miR-132 in islets thereby improving insulin secretion and lowering blood glucose. Mice injected with antagomir-132 for 24 h, had reduced expression of miR-132 expression in islets, decreased blood glucose, and increased insulin secretion. In isolated human islets treated with antagomir-132, insulin secretion from four of six donors increased. Target prediction coupled with analysis of miRNA-messenger RNA expression in human islets revealed DESI2, ARIH1, SLC25A28, DIAPH1, and FOXA1 to be targets of miR-132 that are conserved in both species. Increased expression of these targets was validated in mouse islets after antagomir-132 treatment. In conclusion, we identified a post-transcriptional role for miR-132 in insulin secretion, and demonstrated that systemic antagomir-132 treatment in mice can be used to improve insulin secretion and reduce blood glucose in vivo. Our study is a first step towards utilizing antagomirs as therapeutic agents to modulate islet miRNA levels to improve beta cell function.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
microRNA, Beta cell dysfunction, insulin secretion
in
Nucleic acid therapeutics
volume
29
issue
2
pages
67 - 72
publisher
Mary Ann Liebert, Inc.
external identifiers
  • scopus:85063730021
  • pmid:30672723
ISSN
2159-3337
DOI
10.1089/nat.2018.0763
language
English
LU publication?
yes
id
16ed202f-f77d-4508-ac08-45701ccc4041
date added to LUP
2019-01-28 09:00:22
date last changed
2024-04-01 20:18:22
@article{16ed202f-f77d-4508-ac08-45701ccc4041,
  abstract     = {{<p>Dysfunctional insulin secretion is a hallmark of type 2 diabetes (T2D). Interestingly, several islet microRNAs (miRNAs) are upregulated in T2D, including miR-132. We aimed to investigate whether in vivo treatment with antagomir-132 lowers expression of miR-132 in islets thereby improving insulin secretion and lowering blood glucose. Mice injected with antagomir-132 for 24 h, had reduced expression of miR-132 expression in islets, decreased blood glucose, and increased insulin secretion. In isolated human islets treated with antagomir-132, insulin secretion from four of six donors increased. Target prediction coupled with analysis of miRNA-messenger RNA expression in human islets revealed DESI2, ARIH1, SLC25A28, DIAPH1, and FOXA1 to be targets of miR-132 that are conserved in both species. Increased expression of these targets was validated in mouse islets after antagomir-132 treatment. In conclusion, we identified a post-transcriptional role for miR-132 in insulin secretion, and demonstrated that systemic antagomir-132 treatment in mice can be used to improve insulin secretion and reduce blood glucose in vivo. Our study is a first step towards utilizing antagomirs as therapeutic agents to modulate islet miRNA levels to improve beta cell function.</p>}},
  author       = {{Bijkerk, Roel and Esguerra, Jonathan L S and Ellenbroek, Johanne H and Au, Yu Wah and Hanegraaf, Maaike A J and de Koning, Eelco J and Eliasson, Lena and van Zonneveld, Anton Jan}},
  issn         = {{2159-3337}},
  keywords     = {{microRNA; Beta cell dysfunction; insulin secretion}},
  language     = {{eng}},
  month        = {{01}},
  number       = {{2}},
  pages        = {{67--72}},
  publisher    = {{Mary Ann Liebert, Inc.}},
  series       = {{Nucleic acid therapeutics}},
  title        = {{In Vivo Silencing of MicroRNA-132 Reduces Blood Glucose and Improves Insulin Secretion}},
  url          = {{http://dx.doi.org/10.1089/nat.2018.0763}},
  doi          = {{10.1089/nat.2018.0763}},
  volume       = {{29}},
  year         = {{2019}},
}