ArticleDiabetologia2017
Unravelling the regulation of insulin transport across the brain endothelial cell.
Article in Diabetologia, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
56 citing papers in PubMed, 104 citations in OpenAlex.
- Caveolin-1 at the Crossroads of Diabetes and Alzheimer's Disease: New Mechanisms, Biomarkers, and Therapeutic Opportunities.Biomedicines · 2026Review
- Lipid and polymeric nanocarriers for siRNA delivery to the brain.Journal of controlled release : official journal of the Controlled Release Society · 2025Review
- Bispecific self-assembled peptides as supra-growth factors for preventing endotheliopathy and improving survival of traumatic brain injury in mice.Journal of nanobiotechnology · 2025Article
- Peripheral Inflammation and Insulin Resistance: Their Impact on Blood-Brain Barrier Integrity and Glia Activation in Alzheimer's Disease.International journal of molecular sciences · 2025Review
- Unveiling the mTOR pathway modulation by SGLT2 inhibitors: a novel approach to Alzheimer's disease in type 2 diabetes.Metabolic brain disease · 2025Review
- The Crucial Role of the Blood-Brain Barrier in Neurodegenerative Diseases: Mechanisms of Disruption and Therapeutic Implications.Journal of clinical medicine · 2025Review
- Insulin-inspired hippocampal neuron-targeting technology for protein drug delivery.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- State of the Science on Brain Insulin Resistance and Cognitive Decline Due to Alzheimer's Disease.Aging and disease · 2024Review
- Insulin Signaling Differentially Regulates the Trafficking of Insulin and Amyloid Beta Peptides at the Blood-Brain Barrier.Molecular pharmaceutics · 2024Article
- Bone-derived PDGF-BB enhances hippocampal non-specific transcytosis through microglia-endothelial crosstalk in HFD-induced metabolic syndrome.Journal of neuroinflammation · 2024Article
- Obesity-induced blood-brain barrier dysfunction: phenotypes and mechanisms.Journal of neuroinflammation · 2024Review
- Review
- Effects of dietary soy content on cerebral artery function and behavior in ovariectomized female mice.American journal of physiology. Heart and circulatory physiology · 2024Article
- Hyperinsulinemia Impairs Clathrin-Mediated Endocytosis of the Insulin Receptor and Activation of Endothelial Nitric Oxide Synthase in Brain Endothelial Cells.International journal of molecular sciences · 2023Article
- Cardiometabolic health, menopausal estrogen therapy and the brain: How effects of estrogens diverge in healthy and unhealthy preclinical models of aging.Frontiers in neuroendocrinology · 2023Review
- Engineered nanomaterials that exploit blood-brain barrier dysfunction for delivery to the brain.Advanced drug delivery reviews · 2023Review
- Central nervous system insulin signaling can influence the rate of insulin influx into brain.Fluids and barriers of the CNS · 2023Article
- Drug Permeability: From the Blood-Brain Barrier to the Peripheral Nerve Barriers.Advanced therapeutics · 2023Article
- Cerebrovascular insulin receptors are defective in Alzheimer's disease.Brain : a journal of neurology · 2023Article
- The Role of Insulin Signaling in Hippocampal-Related Diseases: A Focus on Alzheimer's Disease.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
aims/hypothesisFor circulating insulin to act on the brain it must cross the blood-brain barrier (BBB). Remarkably little is known about how circulating insulin crosses the BBB's highly restrictive brain endothelial cells (BECs). Therefore, we examined potential mechanisms regulating BEC insulin uptake, signalling and degradation during BEC transcytosis, and how transport is affected by a high-fat diet (HFD) and by astrocyte activity.
methods
resultsAt physiological insulin concentrations, the IR, not the IGF-1 receptor, facilitated BEC insulin uptake, which required lipid raft-mediated endocytosis, but did not require insulin action on phosphoinositide-3-kinase (PI3K) or mitogen-activated protein kinase kinase (MEK). Feeding rats an HFD for 4 weeks decreased iBEC insulin uptake and increased NF-κB binding activity without affecting insulin PI3K signalling, IR expression or content, or insulin degrading enzyme expression. Using an in vitro BBB (co-culture of iBECs and astrocytes), we found insulin was not degraded during transcytosis, and that stimulating astrocytes with L-glutamate increased transcytosis, while inhibiting nitric oxide synthase decreased insulin transcytosis. CONCLUSIONS/
interpretationInsulin crosses the BBB intact via an IR-specific, vesicle-mediated transport process in the BECs. HFD feeding, nitric oxide inhibition and astrocyte stimulation can regulate BEC insulin uptake and transcytosis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.