ArticlePLoS genetics2013
GLIS3, a susceptibility gene for type 1 and type 2 diabetes, modulates pancreatic beta cell apoptosis via regulation of a splice variant of the BH3-only protein Bim.
Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers, 3 of them syntheses that pooled it.
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Who cites it
104 citing papers in PubMed, 3 syntheses or guidelines pooled it, 180 citations in OpenAlex.
- Childhood body size directly increases type 1 diabetes risk based on a lifecourse Mendelian randomization approach.Nature communications · 2022Pooled it
- Roles of Epigenetic Modifications in the Differentiation and Function of Pancreatic β-Cells.Frontiers in cell and developmental biology · 2020Pooled it
- Genome-wide meta-analysis in alopecia areata resolves HLA associations and reveals two new susceptibility loci.Nature communications · 2015Pooled it
- CTSH regulates β-cell function and disease progression in newly diagnosed type 1 diabetes patients.Proceedings of the National Academy of Sciences of the United States of America · 2014Trial
- Novel association of the obesity risk-allele near Fas Apoptotic Inhibitory Molecule 2 (FAIM2) gene with heart rate and study of its effects on myocardial infarction in diabetic participants of the PREDIMED trial.Cardiovascular diabetology · 2014Trial
- Differential immune- and apoptosis-related gene signatures in pancreatic alpha and beta cells contribute to their fate in type 1 diabetes.Cell death and differentiation · 2026Article
- Genetic recovery in an alpine climate-sensitive pika species during upward treeline shift.BMC genomics · 2026Article
- Identification of distinct functions of GLIS3 in β-cell generation critical to prevention of neonatal diabetes.bioRxiv : the preprint server for biology · 2026Article
- HNF1A and A1CF coordinate a beta cell transcription-splicing axis that is disrupted in type 2 diabetes.Cell metabolism · 2025Article
- A perfect islet: reviewing recent protocol developments and proposing strategies for stem cell derived functional pancreatic islets.Stem cell research & therapy · 2025Review
- Distinct Roles of Common Genetic Variants and Their Contributions to Diabetes: MODY and Uncontrolled T2DM.Biomolecules · 2025Review
- Could hypoxic conditioning augment the potential of mesenchymal stromal cell-derived extracellular vesicles as a treatment for type 1 diabetes?Stem cell research & therapy · 2025Review
- A mechanism-informed deep neural network enables prioritization of regulators that drive cell state transitions.Nature communications · 2025Article
- Linking epigenetic mechanisms of T cell dysfunction with pathophysiology of type 1 diabetes mellitus.Frontiers in immunology · 2025Review
- Article
- Gene-environment interaction in the pathophysiology of type 1 diabetes.Frontiers in endocrinology · 2024Article
- Genome-wide analysis study of gestational diabetes mellitus and related pathogenic factors in a Chinese Han population.BMC pregnancy and childbirth · 2023Article
- Age-dependent genetic regulation of osteoarthritis: independent effects of immune system genes.Arthritis research & therapy · 2023Article
- A Type 1 Diabetes Polygenic Score Is Not Associated With Prevalent Type 2 Diabetes in Large Population Studies.Journal of the Endocrine Society · 2023Article
- Ameliorative Effects of Flavonoids fromNutrients · 2023Article
44 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in human Gli-similar (GLIS) 3 protein cause neonatal diabetes. The GLIS3 gene region has also been identified as a susceptibility risk locus for both type 1 and type 2 diabetes. GLIS3 plays a role in the generation of pancreatic beta cells and in insulin gene expression, but there is no information on the role of this gene on beta cell viability and/or susceptibility to immune- and metabolic-induced stress. GLIS3 knockdown (KD) in INS-1E cells, primary FACS-purified rat beta cells, and human islet cells decreased expression of MafA, Ins2, and Glut2 and inhibited glucose oxidation and insulin secretion, confirming the role of this transcription factor for the beta cell differentiated phenotype. GLIS3 KD increased beta cell apoptosis basally and sensitized the cells to death induced by pro-inflammatory cytokines (interleukin 1β + interferon-γ) or palmitate, agents that may contribute to beta cell loss in respectively type 1 and 2 diabetes. The increased cell death was due to activation of the intrinsic (mitochondrial) pathway of apoptosis, as indicated by cytochrome c release to the cytosol, Bax translocation to the mitochondria and activation of caspases 9 and 3. Analysis of the pathways implicated in beta cell apoptosis following GLIS3 KD indicated modulation of alternative splicing of the pro-apoptotic BH3-only protein Bim, favouring expression of the pro-death variant BimS via inhibition of the splicing factor SRp55. KD of Bim abrogated the pro-apoptotic effect of GLIS3 loss of function alone or in combination with cytokines or palmitate. The present data suggest that altered expression of the candidate gene GLIS3 may contribute to both type 1 and 2 type diabetes by favouring beta cell apoptosis. This is mediated by alternative splicing of the pro-apoptotic protein Bim and exacerbated formation of the most pro-apoptotic variant BimS.
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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.