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http://purl.uniprot.org/citations/22766331http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22766331http://www.w3.org/2000/01/rdf-schema#comment"

Objective

We investigated whether diosgenin, a widely used steroidal sapogenin, exerted protection against palmitate (PA)-induced inflammation and insulin resistance in the endothelium.

Methods

Human umbilical vein endothelial cells (HUVECs) were pretreated with diosgenin for 30 min, and then incubated with 100 μmol/L PA for 30 min or 24 h with or without insulin. IKKβ, p65 phosphorylation, serine phosphorylation of insulin receptor substrate-1 (IRS-1) at S307, tyrosine phosphorylation of IRS-1, Akt and eNOS activation were determined by Western blot analysis. Levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), endothelin-1 (ET-1) and plasminogen activator inhibitor-1 (PAI-1) were measured with ELISA Kits. Intracellular nitric oxide (NO) was viewed with fluorescence microscopy. Effects of diosgenin on insulin-mediated vasodilation was investigated in the isolated rat aortic rings.

Results

Diosgenin significantly reduced PA-enhanced IKKβ and NF-κB phosphorylation with inhibition of TNF-α and IL-6 production in endothelial cells at the concentrations of 0.1, 1 and 10 μmol/L, well demonstrating its anti-inflammatory activity in an IKKβ/NF-κB-dependent fashion. Meanwhile, diosgenin attenuated PA-induced serine phosphorylation (S307) of IRS-1 and restored IRS-1 tyrosine phosphorylation in response to insulin. The beneficial modulation of serine/tyrosine phosphorylation of IRS-1 by diosgenin contributed to the improvement of insulin signaling along PI3K/Akt/eNOS pathways and thereby increased insulin-mediated NO production. Salicylate (5 mmol/L), an inhibitor of IKKβ, showed similar activities as diosgenin. Diosgenin also remarkably inhibited ET-1 and PAI-1 production in the endothelial cells, and markedly restored the loss of insulin-mediated vasodilation in the presence of PA.

Conclusion

The above-mentioned evidence suggests that diosgenin ameliorated endothelial dysfunction involved in insulin resistance through an IKKβ/IRS-1-dependent manner, shows potential application in the treatment for the cardiovascular diseases including atherosclerosis."xsd:string
http://purl.uniprot.org/citations/22766331http://purl.org/dc/terms/identifier"doi:10.1016/j.atherosclerosis.2012.06.012"xsd:string
http://purl.uniprot.org/citations/22766331http://purl.uniprot.org/core/author"Gao X."xsd:string
http://purl.uniprot.org/citations/22766331http://purl.uniprot.org/core/author"Liu B."xsd:string
http://purl.uniprot.org/citations/22766331http://purl.uniprot.org/core/author"Zhao W."xsd:string
http://purl.uniprot.org/citations/22766331http://purl.uniprot.org/core/author"Liu K."xsd:string
http://purl.uniprot.org/citations/22766331http://purl.uniprot.org/core/author"Huang F."xsd:string
http://purl.uniprot.org/citations/22766331http://purl.uniprot.org/core/author"Kou J."xsd:string
http://purl.uniprot.org/citations/22766331http://purl.uniprot.org/core/date"2012"xsd:gYear
http://purl.uniprot.org/citations/22766331http://purl.uniprot.org/core/name"Atherosclerosis"xsd:string
http://purl.uniprot.org/citations/22766331http://purl.uniprot.org/core/pages"350-358"xsd:string
http://purl.uniprot.org/citations/22766331http://purl.uniprot.org/core/title"Diosgenin ameliorates palmitate-induced endothelial dysfunction and insulin resistance via blocking IKKbeta and IRS-1 pathways."xsd:string
http://purl.uniprot.org/citations/22766331http://purl.uniprot.org/core/volume"223"xsd:string
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