miRNAs control insulin content in pancreatic β-cells via downregulation of transcriptional repressors

EMBO J. 2011 Mar 2;30(5):835-45. doi: 10.1038/emboj.2010.361. Epub 2011 Feb 1.


MicroRNAs (miRNAs) were shown to be important for pancreas development, yet their roles in differentiated β-cells remain unclear. Here, we show that miRNA inactivation in β-cells of adult mice results in a striking diabetic phenotype. While islet architecture is intact and differentiation markers are maintained, Dicer1-deficient β-cells show a dramatic decrease in insulin content and insulin mRNA. As a consequence of the change in insulin content, the animals become diabetic. We provide evidence for involvement of a set of miRNAs in regulating insulin synthesis. The specific knockdown of miR-24, miR-26, miR-182 or miR-148 in cultured β-cells or in isolated primary islets downregulates insulin promoter activity and insulin mRNA levels. Further, miRNA-dependent regulation of insulin expression is associated with upregulation of transcriptional repressors, including Bhlhe22 and Sox6. Thus, miRNAs in the adult pancreas act in a new network that reinforces insulin expression by reducing the expression of insulin transcriptional repressors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cell Differentiation
  • Cells, Cultured
  • DEAD-box RNA Helicases / physiology*
  • Down-Regulation
  • Endoribonucleases / physiology*
  • Glucose Intolerance
  • Humans
  • Immunoenzyme Techniques
  • Insulin / genetics*
  • Insulin / metabolism*
  • Insulin-Secreting Cells / cytology
  • Insulin-Secreting Cells / metabolism*
  • Integrases / metabolism
  • Luciferases / metabolism
  • Mice
  • Mice, Knockout
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / physiology*
  • RNA, Messenger / genetics
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Ribonuclease III
  • Transcription, Genetic*


  • Insulin
  • MicroRNAs
  • RNA, Messenger
  • Repressor Proteins
  • Luciferases
  • Cre recombinase
  • Integrases
  • Endoribonucleases
  • Dicer1 protein, mouse
  • Ribonuclease III
  • DEAD-box RNA Helicases