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J Biol Chem. 2015 Aug 14;290(33):20284-94. doi: 10.1074/jbc.M115.658625. Epub 2015 Jul 7.

miR-184 Regulates Pancreatic β-Cell Function According to Glucose Metabolism.

Author information

1
From the Max Delbrueck Center for Molecular Medicine, 13125 Berlin, Germany.
2
Computational and Systems Biology, Biozentrum, University of Basel, 4056 Basel, Switzerland.
3
Institute for Diabetes and Obesity, Helmholtz Centre for Health and Environment and Division of Metabolic Diseases, Technical University Munich, 85748 Munich, Germany.
4
Biological Chemistry Department, Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, 91904 Jerusalem, Israel.
5
Islet cell exocytosis, Lund University Diabetes Center, CRC 91-11, Jan Waldenströms gata 35, 20502 Malmö, Sweden, and.
6
Science for Life Laboratory, Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 17121 Stockholm, Sweden.
7
From the Max Delbrueck Center for Molecular Medicine, 13125 Berlin, Germany, matthew.poy@mdc-berlin.de.

Abstract

In response to fasting or hyperglycemia, the pancreatic β-cell alters its output of secreted insulin; however, the pathways governing this adaptive response are not entirely established. Although the precise role of microRNAs (miRNAs) is also unclear, a recurring theme emphasizes their function in cellular stress responses. We recently showed that miR-184, an abundant miRNA in the β-cell, regulates compensatory proliferation and secretion during insulin resistance. Consistent with previous studies showing miR-184 suppresses insulin release, expression of this miRNA was increased in islets after fasting, demonstrating an active role in the β-cell as glucose levels lower and the insulin demand ceases. Additionally, miR-184 was negatively regulated upon the administration of a sucrose-rich diet in Drosophila, demonstrating strong conservation of this pathway through evolution. Furthermore, miR-184 and its target Argonaute2 remained inversely correlated as concentrations of extracellular glucose increased, underlining a functional relationship between this miRNA and its targets. Lastly, restoration of Argonaute2 in the presence of miR-184 rescued suppression of miR-375-targeted genes, suggesting these genes act in a coordinated manner during changes in the metabolic context. Together, these results highlight the adaptive role of miR-184 according to glucose metabolism and suggest the regulatory role of this miRNA in energy homeostasis is highly conserved.

KEYWORDS:

Argonaute; beta cell (B-cell); glucose metabolism; insulin; insulin secretion; microRNA (miRNA); microRNA mechanism; pancreatic islet

PMID:
26152724
PMCID:
PMC4536436
DOI:
10.1074/jbc.M115.658625
[Indexed for MEDLINE]
Free PMC Article

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