ArticleThe Journal of biological chemistry2019
Down-regulation of the islet-specific zinc transporter-8 (ZnT8) protects human insulinoma cells against inflammatory stress.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 33 citations in OpenAlex.
- Article
- The role of immunoproteasome in diabetes and diabetes-related complications.Genes & diseases · 2026Review
- Zinc accumulation-induced integrated stress response triggers β-cell identity loss.Cell research · 2026Article
- A loss of function variant inmedRxiv : the preprint server for health sciences · 2026Article
- Effects of rs3802177 G/A polymorphism on SLC30A8 mRNA and hsa-miR-183-5p in Malay women with gestational diabetes mellitus.Scientific reports · 2025Article
- Type 2 diabetes mellitus and zinc dysregulation: From basic and epidemiological evidence to interventions.Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) · 2025Review
- Zrt-Irt-like Proteins (ZIP) Family Zinc Transporters: Emerging Players in Pancreatic β Cell Function and Insulin Regulation.The Journal of nutrition · 2025Review
- Roles of zinc and zinc transporters in development, progression, and treatment of inflammatory bowel disease (IBD).Frontiers in nutrition · 2025Review
- Optimized Proteomic Analysis of Insulin Granules From MIN6 Cells Identifies Scamp3, a Novel Regulator of Insulin Secretion and Content.Diabetes · 2024Article
- In vitro reconstitution of transition metal transporters.The Journal of biological chemistry · 2024Review
- Article
- Role of zinc in health and disease.Clinical and experimental medicine · 2024Review
- Cell-Surface Autoantibody Targets Zinc Transporter-8 (ZnT8) for In Vivo β-Cell Imaging and Islet-Specific Therapies.Diabetes · 2023Article
- Zinc Chloride Enhances the Antioxidant Status, Improving the Functional and Structural Organic Disturbances in Streptozotocin-Induced Diabetes in Rats.Medicina (Kaunas, Lithuania) · 2022Article
- ZnT8 loss-of-function accelerates functional maturation of hESC-derived β cells and resists metabolic stress in diabetes.Nature communications · 2022Article
- Review
- Lack of ZnT8 protects pancreatic islets from hypoxia- and cytokine-induced cell death.The Journal of endocrinology · 2022Article
- Synchrotron fluorescence imaging of individual mouse beta-cells reveals changes in zinc, calcium, and iron in a model of low-grade inflammation.Metallomics : integrated biometal science · 2021Article
- Novel autoantibodies to the β-cell surface epitopes of ZnT8 in patients progressing to type-1 diabetes.Journal of autoimmunity · 2021Article
- Zinc.Advances in food and nutrition research · 2021Review
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Zinc transporter-8 (ZnT8) primarily functions as a zinc-sequestrating transporter in the insulin-secretory granules (ISGs) of pancreatic β-cells. Loss-of-function mutations in ZnT8 are associated with protection against type-2 diabetes (T2D), but the protective mechanism is unclear. Here, we developed an in-cell ZnT8 assay to track endogenous ZnT8 responses to metabolic and inflammatory stresses applied to human insulinoma EndoC-βH1 cells. Unexpectedly, high glucose and free fatty acids did not alter cellular ZnT8 levels, but proinflammatory cytokines acutely, reversibly, and gradually down-regulated ZnT8. Approximately 50% of the cellular ZnT8 was localized to the endoplasmic reticulum (ER), which was the primary target of the cytokine-mediated ZnT8 down-regulation. Transcriptome profiling of cytokine-exposed β-cells revealed an adaptive unfolded protein response (UPR) including a marked immunoproteasome activation that coordinately degraded ZnT8 and insulin over a 1,000-fold cytokine concentration range. RNAi-mediated
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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.