ArticleThe Journal of biological chemistry2013
A self-defeating anabolic program leads to β-cell apoptosis in endoplasmic reticulum stress-induced diabetes via regulation of amino acid flux.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed, 115 citations in OpenAlex.
- Article
- Cox10-mediated mitochondrial respiration in brown adipocytes regulates adaptive thermogenesis and systemic metabolism.iScience · 2026Article
- Heavy water labeling reveals metabolic flexibility of amino acid and polyamine pathways in mammalian cells.Communications chemistry · 2026Article
- CHOP promotes the transition to chronic integrated stress response signaling with suppression of hepatocyte identity.bioRxiv : the preprint server for biology · 2026Article
- The Molecular Basis of Amino Acids Sensing.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Squamocin Suppresses Tumor Growth through Triggering an Endoplasmic Reticulum Stress-Associated Degradation of EZH2/MYC Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Boosting the X factor: Increasing XBP1s-mediated ER stress signaling protects motor neurons in ALS/FTD.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Long-term leucine supplementation increases body weight in goats by controlling appetite and muscle protein synthesis under protein-restricted conditions.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2025Article
- Proteomic and metabolomic insights into oxidative stress response activation in mouse embryos generated byHuman reproduction open · 2025Article
- Article
- UBXN1 maintains ER proteostasis and represses UPR activation by modulating translation.EMBO reports · 2024Article
- A beneficial adaptive role for CHOP in driving cell fate selection during ER stress.EMBO reports · 2024Article
- Reduced Expression of Oligodendrocyte Linage-Enriched Transcripts During the Endoplasmic Reticulum Stress/Integrated Stress Response.ASN neuro · 2024Article
- The NERP-4-SNAT2 axis regulates pancreatic β-cell maintenance and function.Nature communications · 2023Article
- Article
- A beneficial adaptive role for CHOP in driving cell fate selection during ER stress.bioRxiv : the preprint server for biology · 2023Article
- Article
- Opposite modulation of functional recovery following contusive spinal cord injury in mice with oligodendrocyte-selective deletions of Atf4 and Chop/Ddit3.Scientific reports · 2023Article
- Determination of in vitro hepatotoxic potencies of a series of perfluoroalkyl substances (PFASs) based on gene expression changes in HepaRG liver cells.Archives of toxicology · 2023Article
- New approach methodologies: A quantitative in vitro to in vivo extrapolation case study with PFASs.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2023Article
23 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 9 institutions in 5 countries.
Funding
Abstract
Endoplasmic reticulum (ER) stress-induced responses are associated with the loss of insulin-producing β-cells in type 2 diabetes mellitus. β-Cell survival during ER stress is believed to depend on decreased protein synthesis rates that are mediated via phosphorylation of the translation initiation factor eIF2α. It is reported here that chronic ER stress correlated with increased islet protein synthesis and apoptosis in β-cells in vivo. Paradoxically, chronic ER stress in β-cells induced an anabolic transcription program to overcome translational repression by eIF2α phosphorylation. This program included expression of amino acid transporter and aminoacyl-tRNA synthetase genes downstream of the stress-induced ATF4-mediated transcription program. The anabolic response was associated with increased amino acid flux and charging of tRNAs for branched chain and aromatic amino acids (e.g. leucine and tryptophan), the levels of which are early serum indicators of diabetes. We conclude that regulation of amino acid transport in β-cells during ER stress involves responses leading to increased protein synthesis, which can be protective during acute stress but can lead to apoptosis during chronic stress. These studies suggest that the increased expression of amino acid transporters in islets can serve as early diagnostic biomarkers for the development of 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.