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ludc web

Lena Eliasson

Principal investigator

ludc web

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

Author

  • 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

Summary, in English

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.

Department/s

  • Diabetes - Islet Cell Exocytosis
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • Department of Clinical Sciences, Malmö

Publishing year

2019-01-23

Language

English

Pages

67-72

Publication/Series

Nucleic acid therapeutics

Volume

29

Issue

2

Document type

Journal article

Publisher

Mary Ann Liebert, Inc.

Topic

  • Endocrinology and Diabetes
  • Pharmaceutical Sciences
  • Biochemistry and Molecular Biology

Keywords

  • microRNA
  • Beta cell dysfunction
  • insulin secretion

Status

Published

Research group

  • Diabetes - Islet Cell Exocytosis

ISBN/ISSN/Other

  • ISSN: 2159-3337