ArticleDiabetologia2012
Cross-talk between the unfolded protein response and nuclear factor-κB signalling pathways regulates cytokine-mediated beta cell death in MIN6 cells and isolated mouse islets.
Article in Diabetologia, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 27 citations in OpenAlex.
- Review
- DOC2b enrichment mitigates proinflammatory cytokine-induced CXCL10 expression by attenuating IKKβ and STAT-1 signaling in human islets.Metabolism: clinical and experimental · 2025Article
- Gypenoside XVII protects against myocardial ischemia and reperfusion injury by inhibiting ER stress-induced mitochondrial injury.Journal of ginseng research · 2021Article
- Polyelectrolytes Formulated with Primary Unconjugated Bile Acid Optimised Pharmacology of Bio-Engineered Implant.Pharmaceutics · 2021Article
- Pro-inflammatory β cell small extracellular vesicles induce β cell failure through activation of the CXCL10/CXCR3 axis in diabetes.Cell reports · 2021Article
- Molecular Machinery and Pathophysiology of Mitochondrial Dynamics.Frontiers in cell and developmental biology · 2021Review
- Adrenomedullin has a cytoprotective role against endoplasmic reticulum stress for pancreatic β-cells in autocrine and paracrine manners.Journal of diabetes investigation · 2020Article
- Elevated β-cell stress levels promote severe diabetes development in mice with MODY4.The Journal of endocrinology · 2020Article
- Chemical Chaperone 4-Phenylbutyric Acid Reduces Cardiac Ischemia/Reperfusion Injury by Alleviating Endoplasmic Reticulum Stress and Oxidative Stress.Medical science monitor : international medical journal of experimental and clinical research · 2016Article
- miR-204 Targets PERK and Regulates UPR Signaling and β-Cell Apoptosis.Molecular endocrinology (Baltimore, Md.) · 2016Article
- Mitochondrial network regulation and its potential interference with inflammatory signals in pancreatic beta cells.Diabetologia · 2016Review
- Par-4/NF-κB Mediates the Apoptosis of Islet β Cells Induced by Glucolipotoxicity.Journal of diabetes research · 2016Article
- Calcium-independent phospholipases A2 and their roles in biological processes and diseases.Journal of lipid research · 2015Review
- Glycemic control in diabetes is restored by therapeutic manipulation of cytokines that regulate beta cell stress.Nature medicine · 2014Article
- N-terminal hydrophobic amino acids of activating transcription factor 5 (ATF5) protein confer interleukin 1β (IL-1β)-induced stabilization.The Journal of biological chemistry · 2014Article
- Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisPancreatic beta cell destruction in type 1 diabetes may be mediated by cytokines such as IL-1β, IFN-γ and TNF-α. Endoplasmic reticulum (ER) stress and nuclear factor-κB (NFκB) signalling are activated by cytokines, but their significance in beta cells remains unclear. Here, we investigated the role of cytokine-induced ER stress and NFκB signalling in beta cell destruction.
methodsIsolated mouse islets and MIN6 beta cells were incubated with IL-1β, IFN-γ and TNF-α. The chemical chaperone 4-phenylbutyric acid (PBA) was used to inhibit ER stress. Protein production and gene expression were assessed by western blot and real-time RT-PCR.
resultsWe found in beta cells that inhibition of cytokine-induced ER stress with PBA unexpectedly potentiated cell death and NFκB-regulated gene expression. These responses were dependent on NFκB activation and were associated with a prolonged decrease in the inhibitor of κB-α (IκBα) protein, resulting from increased IκBα protein degradation. Cytokine-mediated NFκB-regulated gene expression was also potentiated after pre-induction of ER stress with thapsigargin, but not tunicamycin. Both PBA and thapsigargin treatments led to preferential upregulation of ER degradation genes over ER-resident chaperones as part of the adaptive unfolded protein response (UPR). In contrast, tunicamycin activated a balanced adaptive UPR in association with the maintenance of Xbp1 splicing. CONCLUSIONS/
interpretationThese data suggest a novel mechanism by which cytokine-mediated ER stress interacts with NFκB signalling in beta cells, by regulating IκBα degradation. The cross-talk between the UPR and NFκB signalling pathways may be important in the regulation of cytokine-mediated beta cell death.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.