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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.

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


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.


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

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