ArticleThe Journal of biological chemistry2017
Pancreatic β-cell protection from inflammatory stress by the endoplasmic reticulum proteins thrombospondin 1 and mesencephalic astrocyte-derived neutrotrophic factor (MANF).
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 46 citations in OpenAlex.
- Elevated MANF expression in β cells protects mice from streptozotocin-induced diabetes by attenuating islet stress and immunogenicity.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- THBS1: a biomarker for PCOS and its role in pathogenesis via the PI3K/AKT signaling pathway.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Article
- Hexavalent Chromium Toxicity in the Pancreas: A Study on the Protective Effects ofInternational journal of molecular sciences · 2026Article
- Functional genomics reveals mediators of beta cell survival in ER stress and type 2 diabetes risk.bioRxiv : the preprint server for biology · 2026Article
- The Putative Antidiabetic Effect ofInternational journal of molecular sciences · 2025Review
- The role of endothelial cells in pancreatic islet development, transplantation and culture.Frontiers in cell and developmental biology · 2025Review
- Emerging functions of thrombospondin-1 in immunity.Seminars in cell & developmental biology · 2024Review
- Navigating the Landscape of MANF Research: A Scientometric Journey with CiteSpace Analysis.Cellular and molecular neurobiology · 2023Review
- Feeding-induced hepatokines and crosstalk with multi-organ: A novel therapeutic target for Type 2 diabetes.Frontiers in endocrinology · 2023Review
- MANF in POMC Neurons Promotes Brown Adipose Tissue Thermogenesis and Protects Against Diet-Induced Obesity.Diabetes · 2022Article
- O-fucosylation stabilizes the TSR3 motif in thrombospondin-1 by interacting with nearby amino acids and protecting a disulfide bond.The Journal of biological chemistry · 2022Article
- UPR Responsive GenesFrontiers in cellular neuroscience · 2022Review
- The Pancreatic ß-cell Response to Secretory Demands and Adaption to Stress.Endocrinology · 2021Review
- Functional characterization of T2D-associated SNP effects on baseline and ER stress-responsive β cell transcriptional activation.Nature communications · 2021Article
- The relationship of mesencephalic astrocyte-derived neurotrophic factor with hyperlipidemia in patients with or without type 2 diabetes mellitus.Hormones (Athens, Greece) · 2021Article
- CD47 and thrombospondin-1 regulation of mitochondria, metabolism, and diabetes.American journal of physiology. Cell physiology · 2021Review
- MANF: A Novel Endoplasmic Reticulum Stress Response Protein-The Role in Neurological and Metabolic Disorders.Oxidative medicine and cellular longevity · 2021Review
- The KINGSDiabetes · 2020Article
- Trophic activities of endoplasmic reticulum proteins CDNF and MANF.Cell and tissue research · 2020Review
- Thrombospondin-1 in maladaptive aging responses: a concept whose time has come.American journal of physiology. Cell physiology · 2020Review
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cytokine-induced endoplasmic reticulum (ER) stress is one of the molecular mechanisms underlying pancreatic β-cell demise in type 1 diabetes. Thrombospondin 1 (THBS1) was recently shown to promote β-cell survival during lipotoxic stress. Here we show that ER-localized THBS1 is cytoprotective to rat, mouse, and human β-cells exposed to cytokines or thapsigargin-induced ER stress. THBS1 confers cytoprotection by maintaining expression of mesencephalic astrocyte-derived neutrotrophic factor (MANF) in β-cells and thereby prevents the BH3-only protein BIM (BCL2-interacting mediator of cell death)-dependent triggering of the mitochondrial pathway of apoptosis. Prolonged exposure of β-cells to cytokines or thapsigargin leads to THBS1 and MANF degradation and loss of this prosurvival mechanism. Approaches that sustain intracellular THBS1 and MANF expression in β-cells should be explored as a cytoprotective strategy in type 1 diabetes.
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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.