ArticleCNS neuroscience & therapeutics2016
Hyperglycemia Increases the Production of Amyloid Beta-Peptide Leading to Decreased Endothelial Tight Junction.
Article in CNS neuroscience & therapeutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 69 citations in OpenAlex.
- The microcirculation, the blood-brain barrier, and the neurovascular unit in health and Alzheimer disease: The aberrant pericyte is a central player.Pharmacological reviews · 2025Review
- Mesenchymal Stem Cells Restore Endothelial Integrity and Alleviate Emotional Impairments in a Diabetic Mouse Model via Inhibition of MMP-9 Activity.International journal of molecular sciences · 2025Article
- Elevated Triglyceride-Glucose Index as a Risk Stratification Marker for Diabetic Retinopathy in Type 2 Diabetes Mellitus: The Influence of Glycemic Control.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Article
- Melatonin: A potential nighttime guardian against Alzheimer's.Molecular psychiatry · 2025Review
- Supplementation with fish oil reduces αβ 42 burden and shifts αβ precursor protein processing toward non-amyloidogenic pathways in a rat model of hyperglycaemic Alzheimer's disease.Journal of nutritional science · 2025Article
- Role of curcumin on beta-amyloid protein, tau protein, and biochemical and oxidative changes in streptozotocin-induced diabetic rats.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Eucalyptol Ameliorates Retinal Microvascular Defects through Modulating ER Stress and Angiopoietin-Tie Signaling in Diabetic Eyes.International journal of molecular sciences · 2024Article
- Review
- JunB condensation attenuates vascular endothelial damage under hyperglycemic condition.Journal of molecular cell biology · 2024Article
- Endothelial leakiness elicited by amyloid protein aggregation.Nature communications · 2024Article
- Aspirin eugenol ester affects ileal barrier function, inflammatory response and microbiota in broilers under lipopolysaccharide-induced immune stress conditions.Frontiers in veterinary science · 2024Article
- Neuroprotective effects of dipeptidyl peptidase 4 inhibitor on Alzheimer's disease: a narrative review.Frontiers in pharmacology · 2024Review
- Role of Oxidative Stress in Tuberculosis Meningitis Infection in Diabetics.Biomedicines · 2023Review
- Review
- Damage-Associated Molecular Patterns (DAMPs) in Retinal Disorders.International journal of molecular sciences · 2022Review
- Blood-Brain Barrier Breakdown in Relationship to Alzheimer and Vascular Disease.Annals of neurology · 2021Article
- Evolutionary Protection of Krüppel-Like Factors 2 and 4 in the Development of the Mature Hemovascular System.Frontiers in cardiovascular medicine · 2021Article
- Mechanisms and Active Compounds Polysaccharides and Bibenzyls of Medicinal Dendrobiums for Diabetes Management.Frontiers in nutrition · 2021Review
- Cannabinoid-profiled agents improve cell survival via reduction of oxidative stress and inflammation, and Nrf2 activation in a toxic model combining hyperglycemia+AβNeurochemistry international · 2020Article
- Altered Brain Endothelial Cell Phenotype from a Familial Alzheimer Mutation and Its Potential Implications for Amyloid Clearance and Drug Delivery.Stem cell reports · 2020Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsAmyloid beta-peptide (Aβ), the main component of senile plaques in the Alzheimer's disease (AD) brains, is generated from sequential cleavage of amyloid precursor protein (APP) by β- and γ-secretase. Hyperglycemia in diabetes may compromise barrier integrity in endothelial cells (ECs). However, the roles of endothelial APP in response to high glucose (HG) remain to be delineated. The aims of this study were to test whether HG may increase Aβ secretion, thereby leading to heightened paracellular permeability in ECs.
methodsWe determined the effects of HG on production of Aβ, expression of full-length APP, intercellular permeability, and expression levels of specific junctional proteins in human umbilical vein endothelial cells (HUVECs).
resultsHG at 30 mM significantly stimulated expression of full-length APP accompanied by heightened secretion of Aβ1-42, increased paracellular permeability, and attenuated expression of zona occluden-1 (ZO-1), claudin-5, occludin, and junctional adhesion molecule (JAM)-C in HUVECs; all of which were abolished by the γ-secretase inhibitor BMS299897. Exogenous application of Aβ1-42, but not the reverse peptide Aβ42-1, was sufficient to downregulate the expression of the same junction proteins.
conclusionHyperglycemia enhances APP expression with increased Aβ production, which downregulates junctional proteins causing increased intercellular permeability in ECs.
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