Rfx6 maintains the functional identity of adult pancreatic β cells

Cell Rep. 2014 Dec 24;9(6):2219-32. doi: 10.1016/j.celrep.2014.11.033. Epub 2014 Dec 11.


Increasing evidence suggests that loss of β cell characteristics may cause insulin secretory deficiency in diabetes, but the underlying mechanisms remain unclear. Here, we show that Rfx6, whose mutation leads to neonatal diabetes in humans, is essential to maintain key features of functionally mature β cells in mice. Rfx6 loss in adult β cells leads to glucose intolerance, impaired β cell glucose sensing, and defective insulin secretion. This is associated with reduced expression of core components of the insulin secretion pathway, including glucokinase, the Abcc8/SUR1 subunit of KATP channels and voltage-gated Ca(2+) channels, which are direct targets of Rfx6. Moreover, Rfx6 contributes to the silencing of the vast majority of "disallowed" genes, a group usually specifically repressed in adult β cells, and thus to the maintenance of β cell maturity. These findings raise the possibility that changes in Rfx6 expression or activity may contribute to β cell failure in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Channels / genetics
  • Calcium Channels / metabolism
  • Cells, Cultured
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Exocytosis
  • Gene Silencing
  • Glucokinase / genetics
  • Glucokinase / metabolism
  • Glucose / metabolism*
  • Glucose Intolerance / genetics*
  • Insulin / metabolism*
  • Insulin-Secreting Cells / metabolism*
  • Mice
  • Regulatory Factor X Transcription Factors
  • Sulfonylurea Receptors / genetics
  • Sulfonylurea Receptors / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*


  • Abcc8 protein, mouse
  • Calcium Channels
  • DNA-Binding Proteins
  • Insulin
  • Regulatory Factor X Transcription Factors
  • Rfx6 protein, mouse
  • Sulfonylurea Receptors
  • Transcription Factors
  • Glucokinase
  • Glucose

Associated data

  • GEO/GSE59622
  • GEO/GSE62844