ArticleDiabetologia2008
Induction of nuclear factor-kappaB and its downstream genes by TNF-alpha and IL-1beta has a pro-apoptotic role 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 81 papers.
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Who cites it
81 citing papers in PubMed, 156 citations in OpenAlex.
- Effect of diacerein on insulin secretion and metabolic control in drug-naive patients with type 2 diabetes: a randomized clinical trial.Diabetes care · 2011Trial
- Effect of diacerein as an add-on to metformin in patients with type 2 diabetes mellitus and inadequate glycemic control.Archives of endocrinology and metabolismTrial
- The ubiquitin-editing enzyme A20 (TNFAIP3): mechanisms of activation, biological function, diseases and therapeutic targets.Molecular biomedicine · 2026Review
- Kaempferol: advances in biosynthesis, molecular mechanisms, and therapeutic applications.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- The microbiota-gut-brain axis: novel mechanisms and therapeutic frontiers in obesity and type 2 diabetes.NPJ biofilms and microbiomes · 2026Review
- IL-1β priming triggers an adaptive stress response that enhances pancreatic β-cell resilience to subsequent cytotoxic inflammatory insult.Cell death & disease · 2025Article
- DOC2b enrichment mitigates proinflammatory cytokine-induced CXCL10 expression by attenuating IKKβ and STAT-1 signaling in human islets.Metabolism: clinical and experimental · 2025Article
- Bcl-2 and Bcl-xL in Diabetes: Contributions to Endocrine Pancreas Viability and Function.Biomedicines · 2025Review
- Assessment of protein synthesis rate enables metabolic profiling of resident-immune cells of the islets of Langerhans.Frontiers in immunology · 2025Article
- Article
- Tipping-point transition from transient to persistent inflammation in pancreatic islets.NPJ systems biology and applications · 2024Article
- Islet-resident macrophage-derived miR-155 promotes β cell decompensation via targeting PDX1.iScience · 2024Article
- A Supportive Role of Mesenchymal Stem Cells on Insulin-Producing Langerhans Islets with a Specific Emphasis on The Secretome.Biomedicines · 2023Review
- Inhibition of the type 1 diabetes candidate gene PTPN2 aggravates TNF-α-induced human beta cell dysfunction and death.Diabetologia · 2023Article
- The genetic link between systemic autoimmune disorders and temporal lobe epilepsy: A bioinformatics study.Epilepsia open · 2023Article
- Pre-treatment with IL-6 potentiates β-cell death induced by pro-inflammatory cytokines.BMC molecular and cell biology · 2023Article
- How the Innate Immune DNA Sensing cGAS-STING Pathway Is Involved in Apoptosis.International journal of molecular sciences · 2023Review
- The dynamics of cell death patterns and regeneration during acute liver injury in mice.FEBS open bio · 2022Article
- Chemical inducer of regucalcin attenuates lipopolysaccharide-induced inflammatory responses in pancreatic MIN6 β-cells and RAW264.7 macrophages.FEBS open bio · 2022Article
- Mechanisms of Kaempferol in the treatment of diabetes: A comprehensive and latest review.Frontiers in endocrinology · 2022Review
21 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisIL-1beta and TNF-alpha contribute to pancreatic beta cell death in type 1 diabetes. Both cytokines activate the transcription factor nuclear factor-kappaB (NF-kappaB), but recent observations suggest that NF-kappaB blockade prevents IL-1beta + IFN-gamma- but not TNF-alpha + IFN-gamma-induced beta cell apoptosis. The aim of the present study was to compare the effects of IL-1beta and TNF-alpha on cell death and the pattern of NF-kappaB activation and global gene expression in beta cells.
methodsCell viability was measured after exposure to IL-1beta or to TNF-alpha alone or in combination with IFN-gamma, and blockade of NF-kappaB activation or protein synthesis. INS-1E cells exposed to IL-1beta or TNF-alpha in time course experiments were used for IkappaB kinase (IKK) activation assay, detection of p65 NF-kappaB by immunocytochemistry, real-time RT-PCR and microarray analysis.
resultsBlocking NF-kappaB activation protected beta cells against IL-1beta + IFNgamma- or TNFalpha + IFNgamma-induced apoptosis. Blocking de novo protein synthesis did not increase TNF-alpha- or IL-1beta-induced beta cell death, in line with the observations that cytokines induced the expression of the anti-apoptotic genes A20, Iap-2 and Xiap to a similar extent. Microarray analysis of INS-1E cells treated with IL-1beta or TNF-alpha showed similar patterns of gene expression. IL-1beta, however, induced a higher rate of expression of NF-kappaB target genes putatively involved in beta cell dysfunction and death and a stronger activation of the IKK complex, leading to an earlier translocation of NF-kappaB to the nucleus. CONCLUSIONS/
interpretationNF-kappaB activation in beta cells has a pro-apoptotic role following exposure not only to IL-1beta but also to TNF-alpha. The more marked beta cell death induced by IL-1beta is explained at least in part by higher intensity NF-kappaB activation, leading to increased transcription of key target genes.
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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.