In Vivo Silencing of MicroRNA-132 Reduces Blood Glucose and Improves Insulin Secretion
(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.
(Less)
- author
- 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
- organization
- publishing date
- 2019-01-23
- 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
- 2024-07-23 07:58:39
@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}}, }