ArticleThe Journal of biological chemistry2013
Alteration of endoplasmic reticulum lipid rafts contributes to lipotoxicity in pancreatic β-cells.
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 70 papers.
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Who cites it
70 citing papers in PubMed, 116 citations in OpenAlex.
- Biochemical Mechanisms of Cellular Stress Adaptation in the Pathogenesis of Chronic Diseases.Molecules (Basel, Switzerland) · 2026Review
- Integrated Genomic-Metabolomic Analysis for Tri-Categorical Classification of Type 2 Diabetes Status in the Korean Ansan-Ansung Cohort.International journal of molecular sciences · 2025Article
- Dietary phosphorus restriction induced phospholipid deficiency, endoplasmic reticulum stress, inflammatory response and gut microbiota disorders inFrontiers in immunology · 2025Article
- Endoplasmic reticulum stress in diseases.MedComm · 2024Review
- An adipocentric perspective of pancreatic lipotoxicity in diabetes pathogenesis.The Journal of endocrinology · 2024Review
- Plasma Sphingolipid Profile of Healthy Black and White Adults Differs Based on Their Parental History of Type 2 Diabetes.The Journal of clinical endocrinology and metabolism · 2024Article
- A review of the mechanisms of abnormal ceramide metabolism in type 2 diabetes mellitus, Alzheimer's disease, and their co-morbidities.Frontiers in pharmacology · 2024Review
- Endoplasmic Reticulum Stress and Obesity.Advances in experimental medicine and biology · 2024Review
- The expanding organelle lipidomes: current knowledge and challenges.Cellular and molecular life sciences : CMLS · 2023Review
- Cholesterol Redistribution in Pancreatic β-Cells: A Flexible Path to Regulate Insulin Secretion.Biomolecules · 2023Review
- Advances in the Pathophysiology of Thrombosis in Antiphospholipid Syndrome: Molecular Mechanisms and Signaling through Lipid Rafts.Journal of clinical medicine · 2023Review
- Type 2 Diabetes and Alzheimer's Disease: The Emerging Role of Cellular Lipotoxicity.Biomolecules · 2023Review
- The Dark Side of Sphingolipids: Searching for Potential Cardiovascular Biomarkers.Biomolecules · 2023Review
- Pancreatic beta cell ER export in health and diabetes.Frontiers in endocrinology · 2023Review
- Imaging and Manipulation of Plasma Membrane Fatty Acid Clusters Using TOF-SIMS Combined Optogenetics.Cells · 2022Article
- Targeting Ceramides and Adiponectin Receptors in the Islet of Langerhans for Treating Diabetes.Molecules (Basel, Switzerland) · 2022Review
- Proteomic and Bioinformatics Analysis of Membrane Lipid Domains after Brij 98 Solubilization of Uninduced and Phenobarbital-Induced Rat Liver Microsomes: Defining the Membrane Localization of the P450 Enzyme System.Drug metabolism and disposition: the biological fate of chemicals · 2022Article
- Compartmentalization of Sphingolipid metabolism: Implications for signaling and therapy.Pharmacology & therapeutics · 2022Review
- Destabilization of β Cell FIT2 by saturated fatty acids alter lipid droplet numbers and contribute to ER stress and diabetes.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Review
10 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic saturated fatty acid exposure causes β-cell apoptosis and, thus, contributes to type 2 diabetes. Although endoplasmic reticulum (ER) stress and reduced ER-to-Golgi protein trafficking have been implicated, the exact mechanisms whereby saturated fatty acids trigger β-cell death remain elusive. Using mass spectroscopic lipidomics and subcellular fractionation, we demonstrate that palmitate pretreatment of MIN6 β-cells promoted ER remodeling of both phospholipids and sphingolipids, but only the latter was causally linked to lipotoxic ER stress. Thus, overexpression of glucosylceramide synthase, previously shown to protect against defective protein trafficking and ER stress, partially reversed lipotoxic reductions in ER sphingomyelin (SM) content and aggregation of ER lipid rafts, as visualized using Erlin1-GFP. Using both lipidomics and a sterol response element reporter assay, we confirmed that free cholesterol in the ER was also reciprocally modulated by chronic palmitate and glucosylceramide synthase overexpression. This is consistent with the known coregulation and association of SM and free cholesterol in lipid rafts. Inhibition of SM hydrolysis partially protected against ATF4/C/EBP homology protein induction because of palmitate. Our results suggest that loss of SM in the ER is a key event for initiating β-cell lipotoxicity, which leads to disruption of ER lipid rafts, perturbation of protein trafficking, and initiation of ER stress.
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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.