Type 2 & other diabetes

Loss of RREB1 in pancreatic beta cells reduces cellular insulin content and affects endocrine cell gene expression

DiabetologiaPublished Mechanistic study

Authors' conclusion

Together, our results indicate that RREB1 regulates beta cell function by transcriptionally regulating the expression of genes involved in beta cell development and function.

Study context

Population
Zebrafish lacking rreb1a and rreb1b; human beta cell model (EndoC-βH1); Human induced pluripotent stem cell (hiPSC)-derived beta-like cells; donor islets from carriers of RREB1 T2D risk alleles

Main finding

As reported in the abstract

  • Loss of rreb1a and rreb1b in zebrafish supports an in vivo role for RREB1 in beta cell mass, beta cell insulin expression and glucose levels
  • Loss of RREB1 reduced insulin gene expression and cellular insulin content in EndoC-βH1 cells and impaired insulin secretion under prolonged stimulation
  • Transcriptomics of RREB1 knockdown and knockout EndoC-βH1 cells supports RREB1 as a regulator of insulin secretion genes
  • RREB1KO/KO hiPSC differentiation revealed dysregulation of pro-endocrine cell genes, incl. RFX family members
  • Donor islets from carriers of RREB1 T2D risk alleles have altered glucose-stimulated insulin secretion ex vivo

Original publication

Loss of RREB1 in pancreatic beta cells reduces cellular insulin content and affects endocrine cell gene expression. Diabetologia. Published 12 January 2023. doi:10.1007/s00125-022-05856-6

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