ArticleDiabetes2011
Peroxisome-generated hydrogen peroxide as important mediator of lipotoxicity in insulin-producing cells.
Article in Diabetes, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers.
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Who cites it
106 citing papers in PubMed, 223 citations in OpenAlex.
- Metabolomics analysis of type 2 diabetes remission identifies 12 metabolites with predictive capacity: a CORDIOPREV clinical trial study.BMC medicine · 2022Trial
- Review
- Review
- Organelle-specific crosstalk between calcium and redox signaling in pancreatic β-cells in physiology and type 2 diabetes.Frontiers in network physiology · 2026Review
- Triglycerides, Glucose Metabolism, and Type 2 Diabetes.International journal of molecular sciences · 2025Review
- Transient Catalase Immobilization for Cytoprotection during HACS biomaterials science & engineering · 2025Article
- Cynarin Counteracts Lipotoxicity in Pancreatic β-Cells Via Inhibiting Palmitate-Induced Apoptosis and Linoleic Acid-Provoked Ferroptosis.Plant foods for human nutrition (Dordrecht, Netherlands) · 2025Article
- TRIM21-mediated ubiquitination of SQSTM1/p62 abolishes its Ser403 phosphorylation and enhances palmitic acid cytotoxicity.Autophagy · 2025Article
- Pancreatic β-cell Dysfunction and Diabetes.Juntendo medical journal · 2025Review
- Effects of endurance exercise training on endoplasmic reticulum stress in pancreatic islets of obese mice.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2025Article
- Lipotoxicity of palmitic acid is associated with DGAT1 downregulation and abolished by PPARα activation in liver cells.Journal of lipid research · 2024Article
- Effect of reactive oxygen, nitrogen, and sulfur species on signaling pathways in atherosclerosis.Vascular pharmacology · 2024Review
- Article
- The peroxisome: an update on mysteries 3.0.Histochemistry and cell biology · 2024Review
- Didymin protects pancreatic beta cells by enhancing mitochondrial function in high-fat diet-induced impaired glucose tolerance.Diabetology & metabolic syndrome · 2024Article
- TXNIP inhibition in the treatment of type 2 diabetes mellitus: design, synthesis, and biological evaluation of quinazoline derivatives.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- The Physiological and Pathological Role of Acyl-CoA Oxidation.International journal of molecular sciences · 2023Review
- DsbA-L interacting with catalase in peroxisome improves tubular oxidative damage in diabetic nephropathy.Redox biology · 2023Article
- The biochemistry and physiology of long-chain dicarboxylic acid metabolism.The Biochemical journal · 2023Review
- Recent Pharmacological Options in Type 2 Diabetes and Synergic Mechanism in Cardiovascular Disease.International journal of molecular sciences · 2023Review
46 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
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveType 2 diabetes is a complex disease that is accompanied by elevated levels of nonesterified fatty acids (NEFAs), which contribute to β-cell dysfunction and β-cell loss, referred to as lipotoxicity. Experimental evidence suggests that oxidative stress is involved in lipotoxicity. In this study, we analyzed the molecular mechanisms of reactive oxygen species-mediated lipotoxicity in insulin-producing RINm5F cells and INS-1E cells as well as in primary rat islet cells. RESEARCH DESIGN AND
methodsThe toxicity of saturated NEFAs with different chain lengths upon insulin-producing cells was determined by MTT and propidium iodide (PI) viability assays. Catalase or superoxide dismutase overexpressing cells were used to analyze the nature and the cellular compartment of reactive oxygen species formation. With the new H₂O₂-sensitive fluorescent protein HyPer H₂O₂ formation induced by exposure to palmitic acid was determined.
resultsOnly long-chain (>C14) saturated NEFAs were toxic to insulin-producing cells. Overexpression of catalase in the peroxisomes and in the cytosol, but not in the mitochondria, significantly reduced H₂O₂ formation and protected the cells against palmitic acid-induced toxicity. With the HyPer protein, H₂O₂ generation was directly detectable in the peroxisomes of RINm5F and INS-1E insulin-producing cells as well as in primary rat islet cells.
conclusionsThe results demonstrate that H₂O₂ formation in the peroxisomes rather than in the mitochondria are responsible for NEFA-induced toxicity. Therefore, we propose a new concept of fatty acid-induced β-cell lipotoxicity mediated via reactive oxygen species formation through peroxisomal β- oxidation.
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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.