ArticleInvestigative ophthalmology & visual science2015
Lipotoxicity augments glucotoxicity-induced mitochondrial damage in the development of diabetic retinopathy.
Article in Investigative ophthalmology & visual science, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 73 citations in OpenAlex.
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- SIRT6's function in controlling the metabolism of lipids and glucose in diabetic nephropathy.Frontiers in endocrinology · 2023Review
- Association of Triglyceride Glucose Index with Prevalence and Incidence of Diabetic Retinopathy in a Singaporean Population.Clinical ophthalmology (Auckland, N.Z.) · 2023Article
- Research Progress on Mitochondrial Dysfunction in Diabetic Retinopathy.Antioxidants (Basel, Switzerland) · 2022Review
- Regulation of serine palmitoyl-transferase and Rac1-Nox2 signaling in diabetic retinopathy.Scientific reports · 2022Article
- Lipotoxicity as a Barrier for T Cell-Based Therapies.Biomolecules · 2022Review
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- Nutrition Interventions of Herbal Compounds on Cellular Senescence.Oxidative medicine and cellular longevity · 2022Review
- Lipid Droplets Protect Human β-Cells From Lipotoxicity-Induced Stress and Cell Identity Changes.Diabetes · 2021Article
- Regulation of Rac1 transcription by histone and DNA methylation in diabetic retinopathy.Scientific reports · 2021Article
- Diabetic Retinopathy and NADPH Oxidase-2: A Sweet Slippery Road.Antioxidants (Basel, Switzerland) · 2021Review
- Therapeutic potential of curcumin in diabetic retinopathy (Review).International journal of molecular medicine · 2021Review
- Breast cancer-associated skeletal muscle mitochondrial dysfunction and lipid accumulation is reversed by PPARG.American journal of physiology. Cell physiology · 2021Article
- Emerging Roles of Dyslipidemia and Hyperglycemia in Diabetic Retinopathy: Molecular Mechanisms and Clinical Perspectives.Frontiers in endocrinology · 2021Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
purposeAlthough hyperglycemia is the main instigator in the development of diabetic retinopathy, dyslipidemia is also considered to play an important role. In the pathogenesis of diabetic retinopathy, cytosolic NADPH oxidase 2 (Nox2) is activated before retinal mitochondria are damaged. Our aim was to investigate the effect of lipids in the development of diabetic retinopathy.
methodsReactive oxygen species (ROS, by 2',7'-dichlorofluorescein diacetate) and activities of Nox2 (by a lucigenin-based method) and Rac1 (by G-LISA) were quantified in retinal endothelial cells incubated with 50 μM palmitate in 5 mM glucose (lipotoxicity) or 20 mM glucose (glucolipotoxicity) for 6 to 96 hours. Mitochondrial DNA (mtDNA) damage was evaluated by extended-length PCR and its transcription by quantifying cytochrome b transcripts.
resultsWithin 6 hours of exposure of endothelial cells to lipotoxicity, or glucotoxicity (20 mM glucose, without palmitate), significant increase in ROS, Nox2, and Rac1 was observed, which was exacerbated by glucolipotoxic insult. At 48 hours, neither lipotoxicity nor glucotoxicity had any effect on mtDNA and its transcription, but glucolipotoxicity significantly damaged mtDNA and decreased cytochrome b transcripts, and at 96 hours, glucotoxicity and glucolipotoxicity produced similar detrimental effects on mitochondrial damage.
conclusionsAlthough during initial exposure, lipotoxic or glucotoxic insult produces similar increase in ROS, addition of lipotoxicity in a glucotoxic environment further exacerbates ROS production, and also accelerates their damaging effects on mitochondrial homeostasis. Thus, modulation of Nox2 by pharmacological agents in prediabetic patients with dyslipidemia could retard the development of retinopathy before their hyperglycemia is observable.
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