miR-184 regulates pancreatic β-cell function according to glucose metabolism


  • S.G. Tattikota
  • T. Rathjen
  • J. Hausser
  • A. Khedkar
  • U.D. Kabra
  • V.K. Pandey
  • M.D. Sury
  • H.H. Wessels
  • I.G. Mollet
  • L. Eliasson
  • M. Selbach
  • R.P. Zinzen
  • M. Zavolan
  • S. Kadener
  • M. Tschöp
  • M. Jastroch
  • M.R. Friedländer
  • M.N. Poy


  • Journal of Biological Chemistry


  • J Biol Chem 290 (33): 20284-20294


  • In response to fasting or hyperglycemia, the pancreatic {beta}-cell alters its output of secreted insulin; however the pathways governing this adaptive response are not entirely established. While 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 {beta}-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 {beta}-cell as glucose levels lower and the insulin demand ceases. Additionally, miR-184 was negatively regulated upon administration of a sucrose-rich diet in Drosophila demonstrating strong conservation of this pathway through evolution. Furthermore, miR-184 and its target Argonaute2 (Ago2) remained inversely correlated as concentrations of extracellular glucose increased, underlining a functional relationship between this miRNA and its targets. Lastly, restoration of Ago2 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.