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

Bijkerk, Roel; Esguerra, Jonathan L S LU ; Ellenbroek, Johanne H; Au, Yu Wah; Hanegraaf, Maaike A J; de Koning, Eelco J; Eliasson, Lena LU 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
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
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
2019-11-13 05:25:22
@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},
  keyword      = {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},
  volume       = {29},
  year         = {2019},
}