ArticleCell death & disease2018
Dysfunctional autophagy following exposure to pro-inflammatory cytokines contributes to pancreatic β-cell apoptosis.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 79 citations in OpenAlex.
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- Retromer-targeted therapy for neurodegenerative diseases.Molecular neurodegeneration · 2026Review
- Real-time in vivo analysis of murine β cells reveals autophagic flux defects before onset of autoimmune diabetes.Science translational medicine · 2026Article
- Coxsackievirus B infection invokes unique cell-type-specific responses in primary human pancreatic islets.Cell reports · 2025Article
- Hydrogen sulfide aggravates neutrophil infiltration, vascular remodeling and elastase-induced abdominal aortic aneurysm in male mice.Communications medicine · 2025Article
- Longitudinal pathway analysis using structural information with case studies in early type 1 diabetes.Scientific reports · 2025Article
- Unveiling Gestational Diabetes: An Overview of Pathophysiology and Management.International journal of molecular sciences · 2025Review
- Incidence and Risk Factors for Developing Type 2 Diabetes Mellitus After Acute Myocardial Infarction-A Long-Term Follow-Up.Journal of cardiovascular development and disease · 2025Article
- Cell-targeted PD-1 agonists are potent NK-cell inhibitors.Frontiers in immunology · 2025Article
- Inceptor binds to and directs insulin towards lysosomal degradation in β cells.Nature metabolism · 2024Article
- Repositioning the Early Pathology of Type 1 Diabetes to the Extraislet Vasculature.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Article
- Mitochondrial bioenergetics, metabolism, and beyond in pancreatic β-cells and diabetes.Frontiers in molecular biosciences · 2024Review
- Identification of common genes and pathways between type 2 diabetes and COVID-19.Frontiers in genetics · 2024Article
- Crosstalk Between Autophagy and Inflammation in Chronic Cerebral Ischaemia.Cellular and molecular neurobiology · 2023Review
- The inhibition of FKBP5 protects β-cell survival under inflammation stress via AKT/FOXO1 signaling.Cell death discovery · 2023Article
- From Diabetes to Diabetic Complications: Role of Autophagy.Current medical science · 2023Review
- Cathepsin B in programmed cell death machinery: mechanisms of execution and regulatory pathways.Cell death & disease · 2023Review
- β Cell and Autophagy: What Do We Know?Biomolecules · 2023Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Type 1 diabetes (T1D) results from β-cell destruction due to concerted action of both innate and adaptive immune responses. Pro-inflammatory cytokines, such as interleukin-1β and interferon-γ, secreted by the immune cells invading islets of Langerhans, contribute to pancreatic β-cell death in T1D. Cytokine-induced endoplasmic reticulum (ER) stress plays a central role in β-cell demise. ER stress can modulate autophagic response; however, no study addressed the regulation of autophagy during the pathophysiology of T1D. In this study, we document that cytokines activate the AMPK-ULK-1 pathway while inhibiting mTORC1, which stimulates autophagy activity in an ER stress-dependent manner. On the other hand, time-course analysis of LC3-II accumulation in autophagosomes revealed that cytokines block the autophagy flux in an ER stress independent manner, leading to the formation of large dysfunctional autophagosomes and worsening of ER stress. Cytokines rapidly impair lysosome function, leading to lysosome membrane permeabilization, Cathepsin B leakage and lysosomal cell death. Blocking cathepsin activity partially protects against cytokine-induced or torin1-induced apoptosis, whereas blocking autophagy aggravates cytokine-induced CHOP overexpression and β-cell apoptosis. In conclusion, cytokines stimulate the early steps of autophagy while blocking the autophagic flux, which aggravate ER stress and trigger lysosomal cell death. Restoration of autophagy/lysosomal function may represent a novel strategy to improve β-cell resistance in the context of T1D.
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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.