ArticleDiabetologia2023
Loss of RREB1 in pancreatic beta cells reduces cellular insulin content and affects endocrine cell gene expression.
Article in Diabetologia, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- The role of resistance training in improving beta-cell function in type 2 diabetes: a systematic review and meta-analysis.BMC endocrine disorders · 2026Pooled it
- Pancreatic organoids and organoid-on-a-chip platforms: from disease modeling to precision therapy.Journal of translational medicine · 2026Review
- Nephron-associated Support Cell Transcriptional Plasticity Expands in Hypertension.bioRxiv : the preprint server for biology · 2026Article
- Rheb1 signaling and the fate of pancreatic β cells: Toward a new frontier in diabetes therapy.World journal of diabetes · 2025Article
- Insulin levels at 18-20 gestational weeks in pregnant women with obesity are associated with newborn abdominal fat deposition and DNA methylation in cord blood.Clinical epigenetics · 2025Article
- Molecular correlates of glycine receptor activity in human β cells.Molecular metabolism · 2025Article
- The Multifaceted Roles of Zinc Finger Proteins in Pluripotency and Reprogramming.International journal of molecular sciences · 2025Review
- Functionally characterizing obesity-susceptibility genes using CRISPR/Cas9, in vivo imaging and deep learning.Scientific reports · 2025Article
- Loss ofbioRxiv : the preprint server for biology · 2024Article
- Noninvasive assessment of organ-specific and shared pathways in multi-organ fibrosis using T1 mapping.Nature medicine · 2024Article
- Review
- Integrative single-cell characterization of a frugivorous and an insectivorous bat kidney and pancreas.Nature communications · 2024Article
- Zebrafish regulatory genomic resources for disease modelling and regeneration.Disease models & mechanisms · 2023Article
- Moderate-intensity endurance training improves late phase β-cell function in adults with type 2 diabetes.iScience · 2023Article
Corrections and comments
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Authors and funding
22 authors at 5 institutions in 4 countries.
Funding
Abstract
aims/hypothesisGenome-wide studies have uncovered multiple independent signals at the RREB1 locus associated with altered type 2 diabetes risk and related glycaemic traits. However, little is known about the function of the zinc finger transcription factor Ras-responsive element binding protein 1 (RREB1) in glucose homeostasis or how changes in its expression and/or function influence diabetes risk.
methodsA zebrafish model lacking rreb1a and rreb1b was used to study the effect of RREB1 loss in vivo. Using transcriptomic and cellular phenotyping of a human beta cell model (EndoC-βH1) and human induced pluripotent stem cell (hiPSC)-derived beta-like cells, we investigated how loss of RREB1 expression and activity affects pancreatic endocrine cell development and function. Ex vivo measurements of human islet function were performed in donor islets from carriers of RREB1 type 2 diabetes risk alleles.
resultsCRISPR/Cas9-mediated loss of rreb1a and rreb1b function in zebrafish supports an in vivo role for the transcription factor in beta cell mass, beta cell insulin expression and glucose levels. Loss of RREB1 also reduced insulin gene expression and cellular insulin content in EndoC-βH1 cells and impaired insulin secretion under prolonged stimulation. Transcriptomic analysis of RREB1 knockdown and knockout EndoC-βH1 cells supports RREB1 as a novel regulator of genes involved in insulin secretion. In vitro differentiation of RREB1 CONCLUSIONS/
interpretationTogether, our results indicate that RREB1 regulates beta cell function by transcriptionally regulating the expression of genes involved in beta cell development and function.
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