ArticleJournal of autoimmunity2017
Interferon alpha impairs insulin production in human beta cells via endoplasmic reticulum stress.
Article in Journal of autoimmunity, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 2 of them syntheses that pooled it.
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The trial behind it
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Who cites it
51 citing papers in PubMed, 2 syntheses or guidelines pooled it, 65 citations in OpenAlex.
- Molecular Footprints of the Immune Assault on Pancreatic Beta Cells in Type 1 Diabetes.Frontiers in endocrinology · 2020Pooled it
- Associations between cytotoxic T-lymphocyte-associated antigen 4 gene polymorphisms and diabetes mellitus: a meta-analysis of 76 case-control studies.Bioscience reports · 2019Pooled it
- Insulin production is sustained during DNA damage-mediated senescence in adult human beta cells.Diabetologia · 2026Article
- Plasma EV miR-186-5p as an Early Biomarker and Regulator of IFN-α-Mediated Oxidative and β-Cell Dysfunction in Prediabetes.Antioxidants (Basel, Switzerland) · 2026Article
- Molecular and Inflammatory Etiologies of β-Cell Dysfunction in Type 1 Diabetes.Physiology (Bethesda, Md.) · 2025Review
- Review of Promising Off-Label Use of Deucravacitinib.International journal of molecular sciences · 2025Review
- The Role of Type I Interferons in Tuberculosis and in Tuberculosis-Risk-Associated Comorbidities.Infectious disease reports · 2025Review
- The immunology of type 1 diabetes.Nature reviews. Immunology · 2024Review
- Disrupted RNA editing in beta cells mimics early-stage type 1 diabetes.Cell metabolism · 2024Article
- Mechanisms underlying the development of type 1 diabetes in ART-treated people living with HIV: an enigmatic puzzle.Frontiers in immunology · 2024Review
- Article
- Deucravacitinib, a tyrosine kinase 2 pseudokinase inhibitor, protects human EndoC-βH1 β-cells against proinflammatory insults.Frontiers in immunology · 2023Article
- High-resolution analysis of the cytosolic CaAmerican journal of physiology. Endocrinology and metabolism · 2023Article
- Review
- In-Hospital Hyperglycemia Is Associated With Worse Outcomes in Patients Admitted With COVID-19.Diabetes care · 2022Article
- Persistent coxsackievirus B infection and pathogenesis of type 1 diabetes mellitus.Nature reviews. Endocrinology · 2022Review
- Attenuation of Olanzapine-Induced Endoplasmic Reticulum Stress Improves Insulin Secretion in Pancreatic Beta Cells.Metabolites · 2022Article
- Article
- Fighting Enteroviral Infections to Prevent Type 1 Diabetes.Microorganisms · 2022Article
- Expression of Human Mutant Preproinsulins Induced Unfolded Protein Response,International journal of molecular sciences · 2021Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Despite substantial advances in the research exploring the pathogenesis of Type 1 Diabetes (T1D), the pathophysiological mechanisms involved remain unknown. We hypothesized in this study that interferon alpha (IFNα) participates in the early stages of T1D development by triggering endoplasmic reticulum (ER) stress. To verify our hypothesis, human islets and human EndoC-βH1 cells were exposed to IFNα and tested for ER stress markers, glucose stimulated insulin secretion (GSIS) and insulin content. IFNα treatment induced upregulation of ER stress markers including Binding immunoglobulin Protein, phospho-eukaryotic translation initiation factor 2α, spliced- X-box binding protein-1, C/EBP homologous protein and activating transcription factor 4. Intriguingly, IFNα treatment did not impair GSIS but significantly decreased insulin production in both human islets and EndoC-βH1 cells. Furthermore, IFNα decreased the expression of both proinsulin convertase 1 and proinsulin convertase 2, suggesting an altered functional state of the beta cells characterized by a slower proinsulin-insulin conversion. Pretreatment of both human islets and EndoC-βH1 cells with chemical chaperones 4-phenylbutyric acid and tauroursodeoxycholic acid completely prevented IFNα effects, indicating an ER stress-mediated impairment of insulin production. We demonstrated for the first time that IFNα elicits ER stress in human beta cells providing a novel mechanistic role for this virus-induced cytokine in the development of T1D. Compounds targeting molecular processes altered in ER-stressed beta cells could represent a potential therapeutic strategy to prevent IFNα-induced beta cell dysfunction in the early onset of T1D.
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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 OpenQuestion graph.