ArticleDiabetes2006
Diabetes alters sphingolipid metabolism in the retina: a potential mechanism of cell death in diabetic retinopathy.
Article in Diabetes, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
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Who cites it
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 101 citations in OpenAlex.
- Implications of Diabetes-Induced Altered Metabolites on Retinal Neurodegeneration.Frontiers in neuroscience · 2022Pooled it
- Integrating mass spectrometry imaging and data-driven segmentation for spatial metabolic mapping of diabetic eye disease.Journal of pharmaceutical analysis · 2026Article
- Systemic strategies to prevent early diabetic retinopathy: targeting polyunsaturated fatty acid metabolism and eicosanoid signaling.Frontiers in medicine · 2026Review
- Lipidomic analysis of vitreous humor derived from patients with proliferative diabetic retinopathy.BMC ophthalmology · 2025Article
- Metabolomics analysis uncovers metabolic changes and remodeling of anti-VEGF therapy on macular edema.Eye and vision (London, England) · 2025Article
- Novel High-Resolution Lipidomes Could Serve as New Biomarkers for Diabetic Retinopathy: A Bidirectional and Mediated Mendelian Randomization Study.Journal of cellular and molecular medicine · 2025Article
- Enzymes of sphingolipid metabolism as transducers of metabolic inputs.Biochemical Society transactions · 2024Review
- Lipidomic studies revealing serological markers associated with the occurrence of retinopathy in type 2 diabetes.Journal of translational medicine · 2024Article
- Whole transcriptome mapping reveals the lncRNA regulatory network of TFP5 treatment in diabetic nephropathy.Genes & genomics · 2024Article
- Gut Microbiota in Patients with Prediabetes.Nutrients · 2024Article
- Untargeted and temporal analysis of retinal lipidome in bacterial endophthalmitis.Prostaglandins & other lipid mediators · 2024Review
- Adiposomes from Obese-Diabetic Individuals Promote Endothelial Dysfunction and Loss of Surface Caveolae.Cells · 2023Article
- Proteomic analysis of diabetic retinas.Frontiers in endocrinology · 2023Article
- Article
- Evaluation of sphingolipid metabolism on diabetic retinopathy.Indian journal of ophthalmology · 2021Article
- Diminished retinal complex lipid synthesis and impaired fatty acid β-oxidation associated with human diabetic retinopathy.JCI insight · 2021Article
- In-depth transcriptomic analysis of human retina reveals molecular mechanisms underlying diabetic retinopathy.Scientific reports · 2021Article
- Absence of retbindin blocks glycolytic flux, disrupts metabolic homeostasis, and leads to photoreceptor degeneration.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Role of ceramides in the pathogenesis of diabetes mellitus and its complications.Journal of diabetes and its complications · 2021Review
- Diabetic photoreceptors: Mechanisms underlying changes in structure and function.Visual neuroscience · 2020Review
6 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
8 authors at 5 institutions in 1 country.
Funding
Abstract
Dysregulated sphingolipid metabolism causes neuronal cell death and is associated with insulin resistance and diseases. Thus, we hypothesized that diabetes-induced changes in retinal sphingolipid metabolism may contribute to neuronal pathologies in diabetic retinopathy. ESI-MS/MS was used to measure ceramide content and ceramide metabolites in whole retinas after 2, 4, and 8 weeks of streptozotocin-induced diabetes. After 4 and 8 weeks of diabetes, a approximately 30% decrease in total ceramide content was observed, concomitant with a significant approximately 30% increase in glucosylceramide levels in fed diabetic rats compared with their age-matched controls. Acute insulin therapy as well as a short-term lowering of glucose via fasting did not affect the increase in glucosylceramide composition. To assess the putative biological consequences of the increase in glucosylceramide composition, R28 retinal neurons were treated with glucosylceramide synthase inhibitors. Inhibiting glycosphingolipid metabolism increased insulin sensitivity in retinal neurons. Glycosphingolipid inhibitors augmented insulin-stimulated p70 S6kinase activity in the presence of inhibitory concentrations of high glucose or glucosamine. Inhibition of glycosphingolipid synthesis also suppressed glucosamine- and interleukin-1beta-induced death. Consistent with these inhibitor studies, pharmacological accumulation of glycosphingolipids increased activation of the endoplasmic reticulum stress response, a putative modulator of insulin resistance and neuronal apoptosis. It is speculated that an increase in glucosylceramide, and possibly higher-order glycosphingolipids, could contribute to the pathogenesis of diabetic retinopathy by contributing to local insulin resistance, resulting in neuronal cell death. Thus, dysfunctional glycosphingolipid metabolism may contribute to metabolic stress in diabetes, and therapeutic strategies to restore normal sphingolipid metabolism may be a viable approach for treatment of diabetic retinopathy.
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Registered trials
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