Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0011849 (
diabetes
)
277,896
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:The neuropilin-like protein ESDN regulates insulin signaling and sensitivity. 2692 37
