ArticleDiabetes2009
Proinflammatory cytokines activate the intrinsic apoptotic pathway in beta-cells.
Article in Diabetes, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 109 papers.
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Who cites it
109 citing papers in PubMed, 205 citations in OpenAlex.
- Dual Modulation of Prostaglandin E2 Receptors EP3 and EP4 Protects β-Cell Mass in a Model of Aggressive Autoimmune Inflammation.Diabetes · 2026Article
- Inflammatory Cytokines Impair Glucagon Expression and Secretion in Pancreatic α-Cells.Diabetes, obesity & metabolism · 2026Article
- BMP5 signalling in beta cells and the impact on insulin secretion in the context of type 2 diabetes.Diabetologia · 2025Article
- Natural Products as Modulators of Iron Metabolism and Ferroptosis in Diabetes and Its Complications.Nutrients · 2025Review
- Isolated Pancreatic Islet Treatment and Apoptosis Measurement.Journal of visualized experiments : JoVE · 2025Article
- RISING STARS: Evidence for established and emerging forms of β-cell death.The Journal of endocrinology · 2024Review
- RTA-408 Regulates p-NF-κB/TSLP/STAT5 Signaling to Ameliorate Nociceptive Hypersensitivity in Chronic Constriction Injury Rats.Molecular neurobiology · 2024Article
- The brain cytokine orchestra in multiple sclerosis: from neuroinflammation to synaptopathology.Molecular brain · 2024Review
- Apolipoprotein L genes are novel mediators of inflammation in beta cells.Diabetologia · 2024Article
- A Supportive Role of Mesenchymal Stem Cells on Insulin-Producing Langerhans Islets with a Specific Emphasis on The Secretome.Biomedicines · 2023Review
- Unveiling nanoscale optical signatures of cytokine-induced β-cell dysfunction.Scientific reports · 2023Article
- Atf3 defines a population of pulmonary endothelial cells essential for lung regeneration.eLife · 2023Article
- Review
- Molecular Evaluation of the Impact of Polymorphic Variants in Apoptotic (Current issues in molecular biology · 2023Article
- Protective Effects of Hemp (Molecules (Basel, Switzerland) · 2023Article
- Editorial: Cytokines, novel cell death models and pathways in cardiovascular diseases.Frontiers in cardiovascular medicine · 2023Article
- Influence of Inhibition of COX-2-Dependent Lipid Metabolism on Regulation of UVB-Induced Keratinocytes Apoptosis by Cannabinoids.Biomolecules · 2022Article
- Article
- The Role of Autophagy and Apoptosis in Neuropathic Pain Formation.International journal of molecular sciences · 2022Review
- Nephropathic Cystinosis: Pathogenic Roles of Inflammation and Potential for New Therapies.Cells · 2022Review
49 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveProinflammatory cytokines are cytotoxic to beta-cells and have been implicated in the pathogenesis of type 1 diabetes and islet graft failure. The importance of the intrinsic mitochondrial apoptotic pathway in cytokine-induced beta-cell death is unclear. Here, cytokine activation of the intrinsic apoptotic pathway and the role of the two proapoptotic Bcl-2 proteins, Bad and Bax, were examined in beta-cells. RESEARCH DESIGN AND
methodsHuman and rat islets and INS-1 cells were exposed to a combination of proinflammatory cytokines (interleukin-1beta, interferon-gamma, and/or tumor necrosis factor-alpha). Activation of Bad was determined by Ser136 dephosphorylation, mitochondrial stress by changes in mitochondrial metabolic activity and cytochrome c release, downstream apoptotic signaling by activation of caspase-9 and -3, and DNA fragmentation. The inhibitors FK506 and V5 were used to investigate the role of Bad and Bax activation, respectively.
resultsWe found that proinflammatory cytokines induced calcineurin-dependent dephosphorylation of Bad Ser136, mitochondrial stress, cytochrome c release, activation of caspase-9 and -3, and DNA fragmentation. Inhibition of Bad Ser136 dephosphorylation or Bax was found to inhibit cytokine-induced intrinsic proapoptotic signaling.
conclusionsOur findings demonstrate that the intrinsic mitochondrial apoptotic pathway contributes significantly to cytokine-induced beta-cell death and suggest a functional role of calcineurin-mediated Bad Ser136 dephosphorylation and Bax activity in cytokine-induced apoptosis.
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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 Socratic graph.