ArticleEMBO molecular medicine2020
Endothelial Notch signaling controls insulin transport in muscle.
Article in EMBO molecular medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 37 citations in OpenAlex.
- Myovascular Niche: The Role of Endothelial Cells in Skeletal Muscle Health and Disease.Circulation research · 2026Review
- Article
- The stem cell within the vessel wall: multipotent pericytes modulating β-cell function and diabetic complications.Stem cell research & therapy · 2025Review
- Layered double hydroxides for regenerative nanomedicine and tissue engineering: recent advances and future perspectives.Journal of nanobiotechnology · 2025Review
- The potential mechanism of MicroRNA involvement in the regulation of muscle development in weaned piglets by tryptophan and its metabolites.BMC genomics · 2025Article
- Single-cell atlas of human pancreatic islet and acinar endothelial cells in health and diabetes.Nature communications · 2025Article
- Effects of defined voluntary running distances coupled with high-fat diet consumption on the skeletal muscle transcriptome of male mice.Physiological reports · 2025Article
- Type 2 diabetes mellitus in adults: pathogenesis, prevention and therapy.Signal transduction and targeted therapy · 2024 · on this mapReview
- Endothelial Notch1 signaling in white adipose tissue promotes cancer cachexia.Nature cancer · 2023Article
- Notch Signaling in the Vasculature: Angiogenesis and Angiocrine Functions.Cold Spring Harbor perspectives in medicine · 2023Review
- Primary diffuse large B-cell lymphoma of the breast: A retrospective study of outcomes and insulin resistance.Saudi medical journal · 2023Article
- Notch signalling in healthy and diseased vasculature.Open biology · 2022Review
- Notch Signaling and Cross-Talk in Hypoxia: A Candidate Pathway for High-Altitude Adaptation.Life (Basel, Switzerland) · 2022Review
- Targeting the vasculature in cardiometabolic disease.The Journal of clinical investigation · 2022Review
- Modulation of endothelium function by fatty acids.Molecular and cellular biochemistry · 2022Review
- Insulin's actions on vascular tissues: Physiological effects and pathophysiological contributions to vascular complications of diabetes.Molecular metabolism · 2021Review
- Caveolae and Lipid Rafts in Endothelium: Valuable Organelles for Multiple Functions.Biomolecules · 2020Review
- Endothelial Notch signaling controls insulin transport in muscle.EMBO molecular medicine · 2020Article
- Angiogenesis in Adipose Tissue: The Interplay Between Adipose and Endothelial Cells.Frontiers in physiology · 2020Review
Corrections and comments
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Authors and funding
20 authors at 5 institutions in 1 country.
Funding
Abstract
The role of the endothelium is not just limited to acting as an inert barrier for facilitating blood transport. Endothelial cells (ECs), through expression of a repertoire of angiocrine molecules, regulate metabolic demands in an organ-specific manner. Insulin flux across the endothelium to muscle cells is a rate-limiting process influencing insulin-mediated lowering of blood glucose. Here, we demonstrate that Notch signaling in ECs regulates insulin transport to muscle. Notch signaling activity was higher in ECs isolated from obese mice compared to non-obese. Sustained Notch signaling in ECs lowered insulin sensitivity and increased blood glucose levels. On the contrary, EC-specific inhibition of Notch signaling increased insulin sensitivity and improved glucose tolerance and glucose uptake in muscle in a high-fat diet-induced insulin resistance model. This was associated with increased transcription of Cav1, Cav2, and Cavin1, higher number of caveolae in ECs, and insulin uptake rates, as well as increased microvessel density. These data imply that Notch signaling in the endothelium actively controls insulin sensitivity and glucose homeostasis and may therefore represent a therapeutic target for diabetes.
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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.