ArticleAmerican journal of physiology. Heart and circulatory physiology2016
The neuropilin-like protein ESDN regulates insulin signaling and sensitivity.
Article in American journal of physiology. Heart and circulatory physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 21 citations in OpenAlex.
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- Discoidin, CUB and LCCL domain containing 2 modulates angiogenesis by inhibiting VEGF receptor 2 endocytosis in endothelial cells.Journal of molecular medicine (Berlin, Germany) · 2025Article
- Clinical, genomic, and proteomic perspectives in the analysis of comorbid conditions in type 2 diabetes mellitus: a retrospective study.Acta diabetologica · 2025Article
- Differential BMP Signaling Mediates the Interplay Between Genetics and Leaflet Numbers in Aortic Valve Calcification.JACC. Basic to translational science · 2022Article
- Perspectives and potential approaches for targeting neuropilin 1 in SARS-CoV-2 infection.Molecular medicine (Cambridge, Mass.) · 2021Review
- ESDN inhibits melanoma progression by blocking E-selectin expression in endothelial cells via STAT3.Cancer letters · 2021Article
- Transcriptomic Profiling Identifies DCBLD2 as a Diagnostic and Prognostic Biomarker in Pancreatic Ductal Adenocarcinoma.Frontiers in molecular biosciences · 2021Article
- FYN and ABL Regulate the Interaction Networks of the DCBLD Receptor Family.Molecular & cellular proteomics : MCP · 2020Article
- Association of DCBLD2 upregulation with tumor progression and poor survival in colorectal cancer.Cellular oncology (Dordrecht, Netherlands) · 2020Article
- Ocular hypertension suppresses homeostatic gene expression in optic nerve head microglia of DBA/2 J mice.Molecular brain · 2020Article
- Analysis of Virus and Host Proteomes During Productive HSV-1 and VZV Infection in Human Epithelial Cells.Frontiers in microbiology · 2020Article
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- Survival marker genes of colorectal cancer derived from consistent transcriptomic profiling.BMC genomics · 2018Article
- Dynamic multi-site phosphorylation by Fyn and Abl drives the interaction between CRKL and the novel scaffolding receptors DCBLD1 and DCBLD2.The Biochemical journal · 2017Article
- Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Insulin effects on cell metabolism, growth, and survival are mediated by its binding to, and activation of, insulin receptor. With increasing prevalence of insulin resistance and diabetes there is considerable interest in identifying novel regulators of insulin signal transduction. The transmembrane protein endothelial and smooth muscle cell-derived neuropilin-like protein (ESDN) is a novel regulator of vascular remodeling and angiogenesis. Here, we investigate a potential role of ESDN in insulin signaling, demonstrating that Esdn gene deletion promotes insulin-induced vascular smooth muscle cell proliferation and migration. This is associated with enhanced protein kinase B and mitogen-activated protein kinase activation as well as insulin receptor phosphorylation. Likewise, insulin signaling in the liver, muscle, and adipose tissue is enhanced in Esdn(-/-) mice, and these animals exhibit improved insulin sensitivity and glucose homeostasis in vivo. The effect of ESDN on insulin signaling is traced back to its interaction with insulin receptor, which alters the receptor interaction with regulatory adaptor protein-E3 ubiquitin ligase pairs, adaptor protein with pleckstrin homology and Src homology 2 domain-c-Cbl and growth factor receptor bound protein 10-neuronal precursor cell-expressed developmentally downregulated 4. In conclusion, our findings establish ESDN as an inhibitor of insulin receptor signal transduction through a novel regulatory mechanism. Loss of ESDN potentiates insulin's metabolic and mitotic effects and provides insights into a novel therapeutic avenue.
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Registered trials
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