ArticleDiabetes2013
The apoptosis inhibitor ARC alleviates the ER stress response to promote β-cell survival.
Article in Diabetes, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Current Update on Categorization of Migraine Subtypes on the Basis of Genetic Variation: a Systematic Review.Molecular neurobiology · 2024Pooled it
- Ubiquitin E3 Ligases and p53 in Doxorubicin-Induced Cardiotoxicity.International journal of molecular sciences · 2025Review
- Role of apoptosis repressor with caspase recruitment domain in human health and chronic diseases.Annals of medicine · 2024Review
- Inducing and measuring apoptotic cell death in mouse pancreatic β-cells and in isolated islets.STAR protocols · 2022Article
- FOXO1 Is Present in Stomach Epithelium and Determines Gastric Cell Distribution.Gastro hep advances · 2022Article
- Loss of apoptosis repressor with caspase recruitment domain (ARC) worsens high fat diet-induced hyperglycemia in mice.The Journal of endocrinology · 2021Article
- Conversion of the death inhibitor ARC to a killer activates pancreatic β cell death in diabetes.Developmental cell · 2021Article
- Expression of apoptosis repressor with caspase recruitment domain (ARC) in familial adenomatous polyposis (FAP) adenomas and its correlation with DNA mismatch repair proteins, p53, Bcl-2, COX-2 and beta-catenin.Cell communication and signaling : CCS · 2021Article
- Role of apoptosis repressor with caspase recruitment domain (ARC) in cell death and cardiovascular disease.Apoptosis : an international journal on programmed cell death · 2021Review
- Role of apoptosis repressor with caspase recruitment domain (ARC) in cell death and cardiovascular disease.Apoptosis : an international journal on programmed cell death · 2021Review
- Role of apoptosis repressor with caspase recruitment domain (ARC) in cancer.Oncology letters · 2019Review
- Fundamental Mechanisms of Regulated Cell Death and Implications for Heart Disease.Physiological reviews · 2019Review
- Retracted Article: Ligustrazine attenuates renal damage by inhibiting endoplasmic reticulum stress in diabetic nephropathy by inactivating MAPK pathways.RSC advances · 2018Article
- Apoptosis Repressor With Caspase Recruitment Domain Ameliorates Amyloid-Induced β-Cell Apoptosis and JNK Pathway Activation.Diabetes · 2017Article
- ARC is essential for maintaining pancreatic islet structure and β-cell viability during type 2 diabetes.Scientific reports · 2017Article
- Glial cell-line derived neurotrophic factor protects human islets from nutrient deprivation and endoplasmic reticulum stress induced apoptosis.Scientific reports · 2017Article
- A myeloid tumor suppressor role forThe Journal of experimental medicine · 2017Article
- Synthesis, Characterization, and DNA Binding Profile of a Macrocyclic β-Sheet Analogue of ARC Protein.ACS medicinal chemistry letters · 2015Article
- Astragaloside IV attenuates proteinuria in streptozotocin-induced diabetic nephropathy via the inhibition of endoplasmic reticulum stress.BMC nephrology · 2015Article
- Dihydromyricetin prevents cardiotoxicity and enhances anticancer activity induced by adriamycin.Oncotarget · 2015Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Type 2 diabetes involves insulin resistance and β-cell failure leading to inadequate insulin secretion. An important component of β-cell failure is cell loss by apoptosis. Apoptosis repressor with caspase recruitment domain (ARC) is an inhibitor of apoptosis that is expressed in cardiac and skeletal myocytes and neurons. ARC possesses the unusual property of antagonizing both the extrinsic (death receptor) and intrinsic (mitochondria/endoplasmic reticulum [ER]) cell death pathways. Here we report that ARC protein is abundant in cells of the endocrine pancreas, including >99.5% of mouse and 73% of human β-cells. Using genetic gain- and loss-of-function approaches, our data demonstrate that ARC inhibits β-cell apoptosis elicited by multiple inducers of cell death, including ER stressors tunicamycin, thapsigargin, and physiological concentrations of palmitate. Unexpectedly, ARC diminishes the ER stress response, acting distal to protein kinase RNA-like ER kinase (PERK) and inositol-requiring protein 1α, to suppress C/EBP homologous protein (CHOP) induction. Depletion of ARC in isolated islets augments palmitate-induced apoptosis, which is dramatically rescued by deletion of CHOP. These data demonstrate that ARC is a previously unrecognized inhibitor of apoptosis in β-cells and that its protective effects are mediated through suppression of the ER stress response pathway.
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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.