ArticlePloS one2014
Glucolipotoxicity impairs ceramide flow from the endoplasmic reticulum to the Golgi apparatus in INS-1 β-cells.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 35 citations in OpenAlex.
- From Adipose Dysfunction to Multi-Organ Steatosis: Defining the Metabolic Steatotic Axis.Current issues in molecular biology · 2026Review
- LC-MS and High-Throughput Data Processing Solutions for Lipid Metabolic Tracing Using Bioorthogonal Click Chemistry.Angewandte Chemie (International ed. in English) · 2025Article
- Single and Combined Impact of Semaglutide, Tirzepatide, and Metformin on β-Cell Maintenance and Function Under High-Glucose-High-Lipid Conditions: A Comparative Study.International journal of molecular sciences · 2025Article
- Sphingosine 1-Phosphate Stimulates ER to Golgi Ceramide Traffic to Promote Survival in T98G Glioma Cells.International journal of molecular sciences · 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
- Contribution of specific ceramides to obesity-associated metabolic diseases.Cellular and molecular life sciences : CMLS · 2022Review
- Natural Ligand-Mimetic and Nonmimetic Inhibitors of the Ceramide Transport Protein CERT.International journal of molecular sciences · 2022Review
- To Be or Not to Be: The Divergent Action and Metabolism of Sphingosine-1 Phosphate in Pancreatic Beta-Cells in Response to Cytokines and Fatty Acids.International journal of molecular sciences · 2022Review
- Lipid-Induced Adaptations of the Pancreatic Beta-Cell to Glucotoxic Conditions Sustain Insulin Secretion.International journal of molecular sciences · 2021Review
- Sphingosine-1 Phosphate Lyase Regulates Sensitivity of Pancreatic Beta-Cells to Lipotoxicity.International journal of molecular sciences · 2021Article
- Protein Kinases Signaling in Pancreatic Beta-cells Death and Type 2 Diabetes.Advances in experimental medicine and biology · 2021Article
- Review
- Cigarette smoke exposure impairs β-cell function through activation of oxidative stress and ceramide accumulation.Molecular metabolism · 2020Article
- Beyond the cell factory: Homeostatic regulation of and by the UPRScience advances · 2020Review
- The role of ceramides in metabolic disorders: when size and localization matters.Nature reviews. Endocrinology · 2020Review
- Defective endoplasmic reticulum export causes proinsulin misfolding in pancreatic β cells.Molecular and cellular endocrinology · 2019Article
- Protective role of the ELOVL2/docosahexaenoic acid axis in glucolipotoxicity-induced apoptosis in rodent beta cells and human islets.Diabetologia · 2018Article
- Chronic Exposure of Human Endothelial Progenitor Cells to Diabetic Condition Abolished the Regulated Kinetics Activity of Exosomes.Iranian journal of pharmaceutical research : IJPR · 2018Article
- The role of ER stress in lipid metabolism and lipotoxicity.Journal of lipid research · 2016Review
- Sphingosine Kinase 2 and Ceramide Transport as Key Targets of the Natural Flavonoid Luteolin to Induce Apoptosis in Colon Cancer Cells.PloS one · 2015Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Accumulating evidence suggests that glucolipotoxicity, arising from the combined actions of elevated glucose and free fatty acid levels, acts as a key pathogenic component in type II diabetes, contributing to β-cell dysfunction and death. Endoplasmic reticulum (ER) stress is among the molecular pathways and regulators involved in these negative effects, and ceramide accumulation due to glucolipotoxicity can be associated with the induction of ER stress. Increased levels of ceramide in ER may be due to enhanced ceramide biosynthesis and/or decreased ceramide utilization. Here, we studied the effect of glucolipotoxic conditions on ceramide traffic in INS-1 cells in order to gain insights into the molecular mechanism(s) of glucolipotoxicity. We showed that glucolipotoxicity inhibited ceramide utilization for complex sphingolipid biosynthesis, thereby reducing the flow of ceramide from the ER to Golgi. Glucolipotoxicity impaired both vesicular- and CERT-mediated ceramide transport through (1) the decreasing of phospho-Akt levels which in turn possibly inhibits vesicular traffic, and (2) the reducing of the amount of active CERT mainly due to a lower protein levels and increased protein phosphorylation to prevent its localization to the Golgi. In conclusion, our findings provide evidence that glucolipotoxicity-induced ceramide overload in the ER, arising from a defect in ceramide trafficking may be a mechanism that contributes to dysfunction and/or death of β-cells exposed to glucolipotoxicity.
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