In Vivo Silencing of MicroRNA-132 Reduces Blood Glucose and Improves Insulin Secretion
| Autor: | Eelco J.P. de Koning, Johanne H. Ellenbroek, Anton Jan van Zonneveld, Roel Bijkerk, Yu Wah Au, Lena Eliasson, Maaike Hanegraaf, Jonathan L.S. Esguerra |
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| Přispěvatelé: | Hubrecht Institute for Developmental Biology and Stem Cell Research |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Blood Glucose
Hepatocyte Nuclear Factor 3-alpha 0301 basic medicine insulin secretion medicine.medical_specialty endocrine system endocrine system diseases Ubiquitin-Protein Ligases Formins Type 2 diabetes Biochemistry miR-132 Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Downregulation and upregulation In vivo Internal medicine Carbon-Nitrogen Lyases Drug Discovery microRNA Genetics medicine Animals Humans Insulin Gene silencing Antagomir Gene Silencing Cation Transport Proteins Molecular Biology geography geography.geographical_feature_category islet Chemistry Antagomirs Islet medicine.disease antagomir Disease Models Animal MicroRNAs 030104 developmental biology Endocrinology Diabetes Mellitus Type 2 Gene Expression Regulation 030220 oncology & carcinogenesis Molecular Medicine |
| Zdroj: | Nucleic Acid Therapeutics, 29(2), 67-72. Mary Ann Liebert Inc. Nucleic Acid Therapeutics Nucleic Acid Therapeutics, 29(2), 67-72. MARY ANN LIEBERT, INC |
| ISSN: | 2159-3337 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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