ArticleMolecular biology of the cell2015
Clathrin-dependent entry and vesicle-mediated exocytosis define insulin transcytosis across microvascular endothelial cells.
Article in Molecular biology of the cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
49 citing papers in PubMed.
- Palmitoylation calibrates mitochondrial transport of insulin across the endothelium in insulin resistance.bioRxiv : the preprint server for biology · 2026Article
- From oversight to insight: the curious case of the endothelial insulin receptor.Blood vessels, thrombosis & hemostasis · 2026Review
- Nanoparticle-Mediated Transcytosis in Tumor Drug Delivery: Mechanisms, Categories, and Novel Applications.Current drug delivery · 2026Review
- Lipid and polymeric nanocarriers for siRNA delivery to the brain.Journal of controlled release : official journal of the Controlled Release Society · 2025Review
- Dynamic modulation of the blood-brain barrier in the healthy brain.Nature reviews. Neuroscience · 2025Review
- Scaffold-free endocrine tissue engineering: role of islet organization and implications in type 1 diabetes.BMC endocrine disorders · 2025Review
- Apolipoprotein A1 and high-density lipoprotein limit low-density lipoprotein transcytosis by binding SR-B1.Journal of lipid research · 2024Article
- Enhanced macromolecular substance extravasation through the blood-brain barrier via acoustic bubble-cell interactions.Ultrasonics sonochemistry · 2024Article
- SORCS2 activity in pancreatic α-cells safeguards insulin granule formation and release from glucose-stressed β-cells.iScience · 2024Article
- Wearing the Lab: Advances and Challenges in Skin-Interfaced Systems for Continuous Biochemical Sensing.Advances in biochemical engineering/biotechnology · 2024Review
- ANKS1A regulates LDL receptor-related protein 1 (LRP1)-mediated cerebrovascular clearance in brain endothelial cells.Nature communications · 2023Article
- 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
- Mechanobiological Adaptation to Hyperosmolarity Enhances Barrier Function in Human Vascular Microphysiological System.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Dynamic glucose uptake, storage, and release by human microvascular endothelial cells.Molecular biology of the cell · 2022Article
- Activation of NMDA receptors in brain endothelial cells increases transcellular permeability.Fluids and barriers of the CNS · 2022Article
- Capillary Endothelial Insulin Transport: The Rate-limiting Step for Insulin-stimulated Glucose Uptake.Endocrinology · 2022Review
- Approaches to Visualising Endocytosis of LDL-Related Lipoproteins.Biomolecules · 2022Review
- Endocytosis of insulin at the blood-brain barrier.Frontiers in drug delivery · 2022Article
- Age-Dependent Changes in the Plasma and Brain Pharmacokinetics of Amyloid-β Peptides and Insulin.Journal of Alzheimer's disease : JAD · 2022Article
- Aberrant branched-chain amino acid catabolism in cardiovascular diseases.Frontiers in cardiovascular medicine · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
Abstract
Transport of insulin across the microvasculature is necessary to reach its target organs (e.g., adipose and muscle tissues) and is rate limiting in insulin action. Morphological evidence suggests that insulin enters endothelial cells of the microvasculature, and studies with large vessel-derived endothelial cells show insulin uptake; however, little is known about the actual transcytosis of insulin and how this occurs in the relevant microvascular endothelial cells. We report an approach to study insulin transcytosis across individual, primary human adipose microvascular endothelial cells (HAMECs), involving insulin uptake followed by vesicle-mediated exocytosis visualized by total internal reflection fluorescence microscopy. In this setting, fluorophore-conjugated insulin exocytosis depended on its initial binding and uptake, which was saturable and much greater than in muscle cells. Unlike its degradation within muscle cells, insulin was stable within HAMECs and escaped lysosomal colocalization. Insulin transcytosis required dynamin but was unaffected by caveolin-1 knockdown or cholesterol depletion. Instead, insulin transcytosis was significantly inhibited by the clathrin-mediated endocytosis inhibitor Pitstop 2 or siRNA-mediated clathrin depletion. Accordingly, insulin internalized for 1 min in HAMECs colocalized with clathrin far more than with caveolin-1. This study constitutes the first evidence of vesicle-mediated insulin transcytosis and highlights that its initial uptake is clathrin dependent and caveolae independent.
Indexed as
Identifiers
What OpenQuestion holds
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.