ArticleProceedings of the National Academy of Sciences of the United States of America2007
The Fas pathway is involved in pancreatic beta cell secretory function.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 77 citations in OpenAlex.
- Anti-interleukin-1 treatment in patients with rheumatoid arthritis and type 2 diabetes (TRACK): A multicentre, open-label, randomised controlled trial.PLoS medicine · 2019Trial
- Elevated inflammation supra-additively promotes the progression from prediabetes to diabetes: a prospective cohort study.Journal of global health · 2025Article
- Apoptotic cell death in disease-Current understanding of the NCCD 2023.Cell death and differentiation · 2023Review
- Exosomes as biomarkers and therapy in type 2 diabetes mellitus and associated complications.Frontiers in physiology · 2023Review
- Selective ablation of thymic and peripheral Foxp3Frontiers in immunology · 2023Article
- Cask methylation involved in the injury of insulin secretion function caused by interleukin1-β.Journal of cellular and molecular medicine · 2020Article
- Insulin Resistance in Osteoarthritis: Similar Mechanisms to Type 2 Diabetes Mellitus.Journal of nutrition and metabolism · 2020Review
- A Novel Subset of CD95Frontiers in immunology · 2020Article
- Gestational Diabetes Adversely Affects Pancreatic Islet Architecture and Function in the Male Rat Offspring.Endocrinology · 2019Article
- Observational
- sFasL-mediated induction of neutrophil activation in patients with type 2 diabetes mellitus.PloS one · 2018Article
- Fas/Fas-Ligand Interaction As a Mechanism of Immune Homeostasis and β-Cell Cytotoxicity: Enforcement Rather Than Neutralization for Treatment of Type 1 Diabetes.Frontiers in immunology · 2017Article
- SYSTEMIC INTERLEUKIN 1β INHIBITION IN PROLIFERATIVE DIABETIC RETINOPATHY: A Prospective Open-Label Study Using Canakinumab.Retina (Philadelphia, Pa.) · 2016Article
- Monocytes from patients with rheumatoid arthritis and type 2 diabetes mellitus display an increased production of interleukin (IL)-1β via the nucleotide-binding domain and leucine-rich repeat containing family pyrin 3(NLRP3)-inflammasome activation: a possible implication for therapeutic decision in these patients.Clinical and experimental immunology · 2015Article
- Plasma IL-1Ra: linking hyperapoB to risk factors for type 2 diabetes independent of obesity in humans.Nutrition & diabetes · 2015Article
- Effects of inflammation on stem cells: together they strive?EMBO reports · 2015Review
- Fas (CD95) expression in myeloid cells promotes obesity‐induced muscle insulin resistance.EMBO molecular medicine · 2014Article
- Possible protective effect of membrane lipid rafts against interleukin-1β-mediated anti-proliferative effect in INS-1 cells.PloS one · 2014Article
- Protein-mediated interactions of pancreatic islet cells.Scientifica · 2013Review
- TOSO promotes β-cell proliferation and protects from apoptosis.Molecular metabolism · 2012Article
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic beta cell mass and function increase in conditions of enhanced insulin demand such as obesity. Failure to adapt leads to diabetes. The molecular mechanisms controlling this adaptive process are unclear. Fas is a death receptor involved in beta cell apoptosis or proliferation, depending on the activity of the caspase-8 inhibitor FLIP. Here we show that the Fas pathway also regulates beta cell secretory function. We observed impaired glucose tolerance in Fas-deficient mice due to a delayed and decreased insulin secretory pattern. Expression of PDX-1, a beta cell-specific transcription factor regulating insulin gene expression and mitochondrial metabolism, was decreased in Fas-deficient beta cells. As a consequence, insulin and ATP production were severely reduced and only partly compensated for by increased beta cell mass. Up-regulation of FLIP enhanced NF-kappaB activity via NF-kappaB-inducing kinase and RelB. This led to increased PDX-1 and insulin production independent of changes in cell turnover. The results support a previously undescribed role for the Fas pathway in regulating insulin production and release.
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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.