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In Vivo Silencing o...
In Vivo Silencing of MicroRNA-132 Reduces Blood Glucose and Improves Insulin Secretion
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- Bijkerk, Roel (author)
- Leiden University Medical Centre
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- Esguerra, Jonathan L S (author)
- Lund University,Lunds universitet,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Diabetes - Islet Cell Exocytosis,Lund University Research Groups,Skåne University Hospital
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- Ellenbroek, Johanne H (author)
- Leiden University Medical Centre
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- Au, Yu Wah (author)
- Leiden University Medical Centre
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- Hanegraaf, Maaike A J (author)
- Leiden University Medical Centre
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- de Koning, Eelco J (author)
- Leiden University Medical Centre
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- Eliasson, Lena (author)
- Lund University,Lunds universitet,Institutionen för kliniska vetenskaper, Malmö,Medicinska fakulteten,Diabetes - öcellsexocytos,Forskargrupper vid Lunds universitet,Department of Clinical Sciences, Malmö,Faculty of Medicine,Diabetes - Islet Cell Exocytosis,Lund University Research Groups,Skåne University Hospital
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- van Zonneveld, Anton Jan (author)
- Leiden University Medical Centre
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(creator_code:org_t)
- Mary Ann Liebert Inc, 2019
- 2019
- English.
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In: Nucleic acid therapeutics. - : Mary Ann Liebert Inc. - 2159-3337 .- 2159-3345. ; 29:2, s. 67-72
- Related links:
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http://dx.doi.org/10...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Subject headings
Close
- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Keyword
- microRNA
- Beta cell dysfunction
- insulin secretion
Publication and Content Type
- art (subject category)
- ref (subject category)
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