title: miR-184 Regulates Pancreatic β-Cell Function According to Glucose Metabolism.
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.
authors.affiliation: From the Max Delbrueck Center for Molecular Medicine, 13125 Berlin, Germany.
authors.forename: Sudhir G
authors.initials: SG
authors.lastname: Tattikota
authors.affiliation: From the Max Delbrueck Center for Molecular Medicine, 13125 Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Rathjen
authors.affiliation: Computational and Systems Biology, Biozentrum, University of Basel, 4056 Basel, Switzerland.
authors.forename: Jean
authors.initials: J
authors.lastname: Hausser
authors.affiliation: From the Max Delbrueck Center for Molecular Medicine, 13125 Berlin, Germany.
authors.forename: Aditya
authors.initials: A
authors.lastname: Khedkar
authors.affiliation: Institute for Diabetes and Obesity, Helmholtz Centre for Health and Environment and Division of Metabolic Diseases, Technical University Munich, 85748 Munich, Germany.
authors.forename: Uma D
authors.initials: UD
authors.lastname: Kabra
authors.affiliation: Biological Chemistry Department, Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, 91904 Jerusalem, Israel.
authors.forename: Varun
authors.initials: V
authors.lastname: Pandey
authors.affiliation: From the Max Delbrueck Center for Molecular Medicine, 13125 Berlin, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Sury
authors.affiliation: From the Max Delbrueck Center for Molecular Medicine, 13125 Berlin, Germany.
authors.forename: Hans-Hermann
authors.initials: HH
authors.lastname: Wessels
authors.affiliation: Islet cell exocytosis, Lund University Diabetes Center, CRC 91-11, Jan Waldenströms gata 35, 20502 Malmö, Sweden, and.
authors.forename: Inês G
authors.initials: IG
authors.lastname: Mollet
authors.affiliation: Islet cell exocytosis, Lund University Diabetes Center, CRC 91-11, Jan Waldenströms gata 35, 20502 Malmö, Sweden, and.
authors.forename: Lena
authors.initials: L
authors.lastname: Eliasson
authors.affiliation: From the Max Delbrueck Center for Molecular Medicine, 13125 Berlin, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Selbach
authors.affiliation: From the Max Delbrueck Center for Molecular Medicine, 13125 Berlin, Germany.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Zinzen
authors.affiliation: Computational and Systems Biology, Biozentrum, University of Basel, 4056 Basel, Switzerland.
authors.forename: Mihaela
authors.initials: M
authors.lastname: Zavolan
authors.affiliation: Biological Chemistry Department, Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, 91904 Jerusalem, Israel.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kadener
authors.affiliation: Institute for Diabetes and Obesity, Helmholtz Centre for Health and Environment and Division of Metabolic Diseases, Technical University Munich, 85748 Munich, Germany.
authors.forename: Matthias H
authors.initials: MH
authors.lastname: Tschöp
authors.affiliation: Institute for Diabetes and Obesity, Helmholtz Centre for Health and Environment and Division of Metabolic Diseases, Technical University Munich, 85748 Munich, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Jastroch
authors.affiliation: Science for Life Laboratory, Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 17121 Stockholm, Sweden.
authors.forename: Marc R
authors.initials: MR
authors.lastname: Friedländer
authors.affiliation: From the Max Delbrueck Center for Molecular Medicine, 13125 Berlin, Germany, matthew.poy@mdc-berlin.de.
authors.forename: Matthew N
authors.initials: MN
authors.lastname: Poy
mesh_terms: D000818:Animals; D060565:Argonaute Proteins / Q000378:metabolism; D002460:Cell Line; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D007515:Islets of Langerhans / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D008928:Mitochondria / Q000378:metabolism
chemical_list: C526735:Ago2 protein, mouse; D060565:Argonaute Proteins; C552233:MIRN184 microRNA, mouse; D035683:MicroRNAs; D005947:Glucose
keywords: Argonaute; beta cell (B-cell); glucose metabolism; insulin; insulin secretion; microRNA (miRNA); microRNA mechanism; pancreatic islet