ArticleJournal of cell science2008
Initiation and execution of lipotoxic ER stress in pancreatic beta-cells.
Article in Journal of cell science, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 321 papers.
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Who cites it
321 citing papers in PubMed, 587 citations in OpenAlex.
- Metabolic Stress Shifts the Function of KArchiv der Pharmazie · 2026Article
- Loss of Echs1 in neural stem and progenitor cells impairs neurogenesis via ER stress activation and lipid metabolic reprogramming.Nature communications · 2026Article
- The diabetes-associated KDiabetologia · 2026Article
- Long-chain saturated free fatty acids induce pancreatic β-cell lipotoxic stress via HFrontiers in endocrinology · 2026Article
- Palmitate impairs autophagic degradation via oxidative stress/perilysosomal Ca2+ overload/mTORC1 activation pathway in pancreatic β cells.JCI insight · 2025Article
- Role of Circulating Lipids in Mediating the Diabetogenic Effect of Obesity.Biomedicines · 2025Article
- The effects of free fatty acid-free bovine serum albumin and palmitate on pancreatic β-cell function.Islets · 2025Article
- Identification of novel type 1 and type 2 diabetes genes by co-localization of human islet eQTL and GWAS variants with colocRedRibbon.Cell genomics · 2025Article
- Triglycerides, Glucose Metabolism, and Type 2 Diabetes.International journal of molecular sciences · 2025Review
- Functional recovery of islet β cells in human type 2 diabetes: Transcriptome signatures unveil therapeutic approaches.Science advances · 2025Article
- Diabetes mellitus and the key role of endoplasmic reticulum stress in pancreatic β cells.Nature reviews. Endocrinology · 2025Review
- Pharmacological inhibition of tyrosine protein-kinase 2 reduces islet inflammation and delays type 1 diabetes onset in mice.EBioMedicine · 2025Article
- miRNA-642a-3p protects β cells from glucolipotoxicity.Molecular therapy. Nucleic acids · 2025Article
- Article
- Targeting polyunsaturated fatty acids desaturase FADS1 inhibits renal cancer growth via ATF3-mediated ER stress response.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025Article
- Deletion of Tfap2a in hepatocytes and macrophages promotes the progression of hepatocellular carcinoma by regulating SREBP1/FASN/ACC pathway and anti-inflammatory effect of IL10.Cell death & disease · 2025Article
- Unveiling Gestational Diabetes: An Overview of Pathophysiology and Management.International journal of molecular sciences · 2025Review
- Proximity proteomics reveals a mechanism of fatty acid transfer at lipid droplet-mitochondria- endoplasmic reticulum contact sites.Nature communications · 2025Article
- Unfolded protein responses: Dynamic machinery in wound healing.Pharmacology & therapeutics · 2025Review
- E3 ligase substrate adaptor SPOP fine-tunes the UPR of pancreatic β cells.Genes & development · 2025Article
261 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 6 institutions in 4 countries.
Funding
Abstract
Free fatty acids (FFA) cause apoptosis of pancreatic beta-cells and might contribute to beta-cell loss in type 2 diabetes via the induction of endoplasmic reticulum (ER) stress. We studied here the molecular mechanisms implicated in FFA-induced ER stress initiation and apoptosis in INS-1E cells, FACS-purified primary beta-cells and human islets exposed to oleate and/or palmitate. Treatment with saturated and/or unsaturated FFA led to differential ER stress signaling. Palmitate induced more apoptosis and markedly activated the IRE1, PERK and ATF6 pathways, owing to a sustained depletion of ER Ca(2+) stores, whereas the unsaturated FFA oleate led to milder PERK and IRE1 activation and comparable ATF6 signaling. Non-metabolizable methyl-FFA analogs induced neither ER stress nor beta-cell apoptosis. The FFA-induced ER stress response was not modified by high glucose concentrations, suggesting that ER stress in primary beta-cells is primarily lipotoxic, and not glucolipotoxic. Palmitate, but not oleate, activated JNK. JNK inhibitors reduced palmitate-mediated AP-1 activation and apoptosis. Blocking the transcription factor CHOP delayed palmitate-induced beta-cell apoptosis. In conclusion, saturated FFA induce ER stress via ER Ca(2+) depletion. The IRE1 and resulting JNK activation contribute to beta-cell apoptosis. PERK activation by palmitate also contributes to beta-cell apoptosis via CHOP.
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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.