ArticlePharmaceutical research2022
Effect of Insulin Receptor-Knockdown on the Expression Levels of Blood-Brain Barrier Functional Proteins in Human Brain Microvascular Endothelial Cells.
Article in Pharmaceutical research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 26 citations in OpenAlex.
- CDKAL1 dysfunction impairs lysine codon translation in podocytes and accelerates chronic kidney disease.The EMBO journal · 2026Article
- Acute peripheral versus central inhibition of insulin receptors differentially alters cytokine and blood-brain barrier responses to an inflammatory stimulus.Brain, behavior, and immunity · 2026Article
- Insulin in Myenteric Neurons: Time-Dependent and Regional Changes in Type 1 Diabetic Rats.Cells · 2025Article
- Proteome profile differences among human, monkey, and mouse brain microvessels and cultured brain microvascular endothelial cells.Fluids and barriers of the CNS · 2025Article
- ENPP1 induces blood-brain barrier dysfunction and promotes brain metastasis formation in human epidermal growth factor receptor 2-positive breast cancer.Neuro-oncology · 2025Article
- Discovery of Glucose Metabolism-Associated Genes in Neuropathic Pain: Insights from Bioinformatics.International journal of molecular sciences · 2024Article
- Endothelial Dysfunctions in Blood-Brain Barrier Breakdown in Alzheimer's Disease: From Mechanisms to Potential Therapies.CNS neuroscience & therapeutics · 2024Review
- Metabolite transport across central nervous system barriers.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Review
- Proteomic alterations in the brain and blood-brain barrier during brain Aβ accumulation in an APP knock-in mouse model of Alzheimer's disease.Fluids and barriers of the CNS · 2023Article
- Metabolic Profile of Alzheimer's Disease: Is 10-Hydroxy-2-decenoic Acid a Pertinent Metabolic Adjuster?Metabolites · 2023Review
- Development of a method for isolating brain capillaries from a single neonatal mouse brain and comparison of proteomic profiles between neonatal and adult brain capillaries.Fluids and barriers of the CNS · 2023Article
- Interactions of alcohol and combination antiretroviral (cART) drug in diabetic male Sprague Dawley rats: Hippocampal perturbations and toxicosis.Toxicology reports · 2023Article
- Evidence for an alternative insulin transporter at the blood-brain barrier.Aging pathobiology and therapeutics · 2022Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
purposeThe insulin receptor (INSR) mediates insulin signaling to modulate cellular functions. Although INSR is expressed at the blood-brain barrier (BBB), its role in the modulation of BBB function is poorly understood. Therefore, in this study, we aimed to analyze the effect of INSR knockdown on the expression levels of functional proteins at the BBB.
methodsWe established the INSR-knockdown cell line (shINSR) using human cerebral microvascular endothelial cells (hCMEC/D3). The cellular proteome was analyzed using quantitative proteomics.
resultsINSR mRNA and protein expressions were decreased in shINSR cells. The suppression of INSR-mediated signaling in shINSR cells was evaluated. The proteins involved in glycolysis and glycogenolysis were suppressed in shINSR cells. As amyloid-β peptide-related proteins, the expressions of presenilin-1 was increased, and those of the insulin-degrading enzyme and neprilysin were decreased. The expressions of BBB transporters, including the ABCB1/MDR1, ABCG2/BCRP, and SLCO2A1/OATP2A1 were significantly decreased by more than 50% in shINSR cells. The efflux activity of ABCB1/MDR1 was also suppressed. The expressions of the low-density lipoprotein receptor-related protein 1 were significantly increased, and those of the transferrin receptor were significantly decreased in shINSR cells. The expression of claudin-5 was also suppressed in shINSR cells.
conclusionsThe present study suggests that INSR-mediated signaling is involved in the regulation of functional protein expression at the BBB and contributes to the maintenance of BBB function. Changes in the expressions of amyloid-β peptide-related proteins may contribute to the development of cerebral amyloid angiopathy via the suppression of INSR-mediated signaling.
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