ArticleDiabetologia2008
Functional significance of repressor element 1 silencing transcription factor (REST) target genes in pancreatic beta cells.
Article in Diabetologia, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 47 citations in OpenAlex.
- Bridging the Gap Between Static Histology and Dynamic Organ-on-a-Chip Models.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026Review
- Novel Pathogenic Variant Confirms the Association of REST and Jones Syndrome.Clinical genetics · 2026Article
- The cause of Jones syndrome put to REST: a mutation in the REST gene causes gingival fibromatosis and hearing loss.European journal of human genetics : EJHG · 2023Article
- COVID-19 induces new-onset insulin resistance and lipid metabolic dysregulation via regulation of secreted metabolic factors.Signal transduction and targeted therapy · 2021Article
- REST is a major negative regulator of endocrine differentiation during pancreas organogenesis.Genes & development · 2021Article
- Scrt1, a transcriptional regulator of β-cell proliferation identified by differential chromatin accessibility during islet maturation.Scientific reports · 2021Article
- Harnessing the Endogenous Plasticity of Pancreatic Islets: A Feasible Regenerative Medicine Therapy for Diabetes?International journal of molecular sciences · 2021Review
- Transcriptomic and Quantitative Proteomic Profiling Reveals Signaling Pathways Critical for Pancreatic Islet Maturation.Endocrinology · 2020Article
- Loss of RE-1 silencing transcription factor accelerates exocrine damage from pancreatic injury.Cell death & disease · 2020Article
- Endocrine lineage biases arise in temporally distinct endocrine progenitors during pancreatic morphogenesis.Nature communications · 2018Article
- Review
- Neuron-enriched RNA-binding Proteins Regulate Pancreatic Beta Cell Function and Survival.The Journal of biological chemistry · 2017Article
- All mixed up: defining roles for β-cell subtypes in mature islets.Genes & development · 2017Review
- The Importance of REST for Development and Function of Beta Cells.Frontiers in cell and developmental biology · 2017Review
- Regulation of connexin signaling by the epigenetic machinery.Biochimica et biophysica acta · 2016Review
- REST represses a subset of the pancreatic endocrine differentiation program.Developmental biology · 2015Article
- Article
- LKB1 and AMPK differentially regulate pancreatic β-cell identity.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2014Article
- Reduction of connexin36 content by ICER-1 contributes to insulin-secreting cells apoptosis induced by oxidized LDL particles.PloS one · 2013Article
- Specific silencing of the REST target genes in insulin-secreting cells uncovers their participation in beta cell survival.PloS one · 2012Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisThe expression of several neuronal genes in pancreatic beta cells is due to the absence of the transcription factor repressor element 1 (RE-1) silencing transcription factor (REST). The identification of these traits and their functional significance in beta cells has only been partly elucidated. Herein, we investigated the biological consequences of a repression of REST target genes by expressing REST in beta cells.
methodsThe effect of REST expression on glucose homeostasis, insulin content and release, and beta cell mass was analysed in transgenic mice selectively expressing REST in beta cells. Relevant target genes were identified in INS-1E and primary beta cells expressing REST.
resultsTransgenic mice featuring a beta cell-targeted expression of REST exhibited glucose intolerance and reduced beta cell mass. In primary beta cells, REST repressed several proteins of the exocytotic machinery, including synaptosomal-associated protein (SNAP) 25, synaptotagmin (SYT) IV, SYT VII, SYT IX and complexin II; it impaired first and second phases of insulin secretion. Using RNA interference in INS-1E cells, we showed that SYT IV and SYT VII were implicated in the control of insulin release. CONCLUSIONS/
interpretationThe data document the critical role of REST target genes in pancreatic beta cells. Specifically, we provide evidence that the downregulation of these genes is detrimental for the exocytosis of large dense core vesicles, thus contributing to beta cell dysfunction and impaired glucose homeostasis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.