ArticleDiabetologia2013
Pathological endoplasmic reticulum stress mediated by the IRE1 pathway contributes to pre-insulitic beta cell apoptosis in a virus-induced rat model of type 1 diabetes.
Article in Diabetologia, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 40 citations in OpenAlex.
- Elevations in the Fasting Serum Proinsulin-to-C-Peptide Ratio Precede the Onset of Type 1 Diabetes.Diabetes care · 2016Trial
- Diabetes mellitus and the key role of endoplasmic reticulum stress in pancreatic β cells.Nature reviews. Endocrinology · 2025Review
- Emerging role of IRE1α in vascular diseases.Journal of cell communication and signaling · 2024Review
- Endoplasmic reticulum stress in diseases.MedComm · 2024Review
- β Cell Stress and Endocrine Function During T1D: What Is Next to Discover?Endocrinology · 2023Article
- The Role of ER Stress in Diabetes: Exploring Pathological Mechanisms Using Wolfram Syndrome.International journal of molecular sciences · 2022Review
- β-Cell Death in Diabetes: Past Discoveries, Present Understanding, and Potential Future Advances.Metabolites · 2021Review
- A soluble endoplasmic reticulum factor as regenerative therapy for Wolfram syndrome.Laboratory investigation; a journal of technical methods and pathology · 2020Article
- MicroRNA-24 promotes pancreatic beta cells toward dedifferentiation to avoid endoplasmic reticulum stress-induced apoptosis.Journal of molecular cell biology · 2019Article
- Article
- Inflammation-Induced Citrullinated Glucose-Regulated Protein 78 Elicits Immune Responses in Human Type 1 Diabetes.Diabetes · 2018Article
- IRE1α Implications in Endoplasmic Reticulum Stress-Mediated Development and Pathogenesis of Autoimmune Diseases.Frontiers in immunology · 2018Review
- Caspase-4 is essential for saikosaponin a-induced apoptosis acting upstream of caspase-2 and γ-H2AX in colon cancer cells.Oncotarget · 2017Article
- Endoplasmic reticulum stress and inflammation in the central nervous system.Molecular neurodegeneration · 2017Review
- Is a β cell a β cell?Current opinion in endocrinology, diabetes, and obesity · 2017Review
- Intermittent fasting preserves beta-cell mass in obesity-induced diabetes via the autophagy-lysosome pathway.Autophagy · 2017Article
- Article
- Endoplasmic reticulum stress in beta cells and autoimmune diabetes.Current opinion in immunology · 2016Review
- End Sequence Analysis Toolkit (ESAT) expands the extractable information from single-cell RNA-seq data.Genome research · 2016Article
- Biomarkers of β-Cell Stress and Death in Type 1 Diabetes.Current diabetes reports · 2016Review
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6 authors at 2 institutions in 1 country.
Funding
Abstract
aims/hypothesisWe hypothesised that pathological endoplasmic reticulum (ER) stress contributes to beta cell death during development of type 1 diabetes. In this study, we investigated the occurrence of beta cell ER stress and the signalling pathways involved during discrete stages of autoimmune diabetes progression. The virus-inducible BBDR rat model was used to systematically interrogate the three main ER stress signalling pathways (IRE1 [inositol-requiring protein-1], PERK [double-stranded RNA-dependent protein kinase (PKR)-like ER kinase] and ATF6 [activating transcription factor 6]) in pancreatic beta cells during type 1 diabetes development.
methodsER stress and apoptotic markers were assessed by immunoblot analyses of isolated pancreatic islets and immunofluorescence staining of pancreas sections from control and virus-induced rats. Various time points were analysed: (1) early stages preceding the development of insulitis and (2) a late stage during onset and progression of insulitis, which precedes overt hyperglycaemia.
resultsThe IRE1 pathway, including its downstream component X-box-binding protein 1, was specifically activated in pancreatic beta cells of virus-induced rats at early stages preceding the development of insulitis. Furthermore, ER stress-specific pro-apoptotic caspase 12 and effector caspase 3 were also activated at this stage. Activation of PERK and its downstream effector pro-apoptotic CHOP (CCAAT/-enhancer-binding-protein homologous protein), only occurred during late stages of diabetes induction concurrent with insulitis, whereas ATF6 activation in pancreatic beta cells was similar in control and virus-induced rats. CONCLUSIONS/
interpretationActivation of the IRE1 pathway and ER stress-specific pro-apoptotic caspase 12, before the development of insulitis, are indicative of ER stress-mediated beta cell damage. The early occurrence of pathological ER stress and death in pancreatic beta cells may contribute to the initiation and/or progression of virus-induced autoimmune diabetes.
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