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

Roel Bijkerk, Jonathan L S Esguerra, Johanne H Ellenbroek, Yu Wah Au, Maaike A J Hanegraaf, Eelco J de Koning, Lena Eliasson, Anton Jan van Zonneveld

Research output: Contribution to journal/periodicalArticleScientificpeer-review

28 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)67-72
Number of pages6
JournalNucleic Acid Therapeutics
Volume29
Issue number2
DOIs
Publication statusPublished - Apr 2019

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