ArticleEndocrinology2021
Endothelial Insulin Receptors Promote VEGF-A Signaling via ERK1/2 and Sprouting Angiogenesis.
Article in Endocrinology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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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.
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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
20 citing papers in PubMed, 36 citations in OpenAlex.
- Lactylation-related genes contribute to neurological injury and prognosis of acute ischemic stroke based on transcriptome and single-cell sequencing analysis.Cell & bioscience · 2026Article
- Endothelial cell metabolism in cardiovascular physiology and disease.Nature reviews. Cardiology · 2025Review
- Topical insulin meets nanomedicine: a synergy for enhanced skin regeneration.Nanomedicine (London, England) · 2025Article
- Identification of endothelial INSR as an osteosarcoma-related biomarker and therapeutic target based on weighted gene co-expression network analysis.Discover oncology · 2025Article
- Ectopic Expansion of Pulmonary Vasculature in Fibrotic Lung Disease and Lung Adenocarcinoma Marked by Proangiogenic COL15A1+ Endothelial Cells.Pulmonary circulation · 2025Article
- Bone marrow breakout lesions act as key sites for tumor-immune cell diversification in multiple myeloma.Science immunology · 2025Article
- SB218078 inhibits angiogenesis and epithelial-mesenchymal transition in breast cancer.Frontiers in pharmacology · 2025Article
- Review
- Single-Cell RNA Sequencing Reveals the Spatial Heterogeneity and Functional Alteration of Endothelial Cells in Chronic Hepatitis B Infection.International journal of molecular sciences · 2024Article
- Article
- A single nuclear transcriptomic characterisation of mechanisms responsible for impaired angiogenesis and blood-brain barrier function in Alzheimer's disease.Nature communications · 2024Article
- NRP1 interacts with endoglin and VEGFR2 to modulate VEGF signaling and endothelial cell sprouting.Communications biology · 2024Article
- Reduced endothelial caveolin-1 underlies deficits in brain insulin signalling in type 2 diabetes.Brain : a journal of neurology · 2023Article
- Role of insulin signaling and its associated signaling in glomerulus for diabetic kidney disease.Histology and histopathology · 2023Review
- Diabetic macrophage small extracellular vesicles-associated miR-503/IGF1R axis regulates endothelial cell function and affects wound healing.Frontiers in immunology · 2023Article
- VEGFR2 insufficiency enhances phosphotoxicity and undermines Klotho's protection against peritubular capillary rarefaction and kidney fibrosis.American journal of physiology. Renal physiology · 2023Article
- Article
- G-CSF promotes the viability and angiogenesis of injured liver via direct effects on the liver cells.Molecular biology reports · 2022Article
- Somatostatin Primes Endothelial Cells for Agonist-Induced Hyperpermeability and Angiogenesis In Vitro.International journal of molecular sciences · 2022Article
- Pericyte Insulin Receptors Modulate Retinal Vascular Remodeling and Endothelial Angiopoietin Signaling.Endocrinology · 2021Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 2 countries.
Funding
Abstract
Endothelial insulin receptors (Insr) promote sprouting angiogenesis, although the underpinning cellular and molecular mechanisms are unknown. Comparing mice with whole-body insulin receptor haploinsufficiency (Insr+/-) against littermate controls, we found impaired limb perfusion and muscle capillary density after inducing hind-limb ischemia; this was in spite of increased expression of the proangiogenic growth factor Vegfa. Insr+/- neonatal retinas exhibited reduced tip cell number and branching complexity during developmental angiogenesis, which was also found in separate studies of mice with endothelium-restricted Insr haploinsufficiency. Functional responses to vascular endothelial growth factor A (VEGF-A), including in vitro angiogenesis, were also impaired in aortic rings and pulmonary endothelial cells from Insr+/- mice. Human umbilical vein endothelial cells with shRNA-mediated knockdown of Insr also demonstrated impaired functional angiogenic responses to VEGF-A. VEGF-A signaling to Akt and endothelial nitric oxide synthase was intact, but downstream signaling to extracellular signal-reduced kinase 1/2 (ERK1/2) was impaired, as was VEGF receptor-2 (VEGFR-2) internalization, which is required specifically for signaling to ERK1/2. Hence, endothelial insulin receptors facilitate the functional response to VEGF-A during angiogenic sprouting and are required for appropriate signal transduction from VEGFR-2 to ERK1/2.
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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.