RGD Reference Report - Resveratrol inhibits inflammation and ameliorates insulin resistant endothelial dysfunction via regulation of AMP-activated protein kinase and sirtuin 1 activities. - Rat Genome Database

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Resveratrol inhibits inflammation and ameliorates insulin resistant endothelial dysfunction via regulation of AMP-activated protein kinase and sirtuin 1 activities.

Authors: Liu, Z  Jiang, C  Zhang, J  Liu, B  Du, Q 
Citation: Liu Z, etal., J Diabetes. 2016 May;8(3):324-335. doi: 10.1111/1753-0407.12296. Epub 2015 May 6.
RGD ID: 11075079
Pubmed: PMID:25850408   (View Abstract at PubMed)
DOI: DOI:10.1111/1753-0407.12296   (Journal Full-text)

BACKGROUND: Resveratrol is a phytoalexin with beneficial effects on human health. The aim of the present study was to investigate the effects of resveratrol on endothelial dysfunction involved in insulin signaling and inflammation. METHODS: Endothelial cells were stimulated with palmitate (PA) to induce insulin resistance characterized by a loss of insulin-mediated nitric oxide (NO) production. Diabetes was induced in rats by fructose feeding. The effects of resveratrol and the mechanisms involved were investigated using an aortic relaxation assay and Western blot analysis. RESULTS: In endothelial cells, 0.1-10 mumol/L resveratrol suppressed IkappaB kinase beta (IKKbeta)/nuclear factor-kappaB phosphorylation, as well as tumor necrosis factor-alpha and interleukin-6 production, and restored the insulin receptor substrate-1 (Irs-1)/Akt/endothelial NO synthase signaling pathway. Furthermore, resveratrol effectively inhibited the mitogenic actions of insulin by decreasing the secretion of endothelin-1 and plasminogen activator inhibitor-1. It also positively regulated AMP-activated kinase (AMPK) and sirtuin 1 (SIRT1) activation, which contributed to the inhibition of inflammation implicated in endothelial insulin resistance. Stimulation with PA and long term-fructose feeding impaired insulin-mediated vessel dilation in rat aorta, whereas pretreatment of aortic rings with resveratrol (0.1-10 mumol/L) or treatment of rats with 5 or 20 mg/kg resveratrol counteracted these changes. CONCLUSION: The results indicate that resveratrol inhibits inflammation and facilitates insulin phosphatidylinositol 3-kinase signaling by beneficial modulation of IRS-1 function partly via regulation of AMPK and SIRT1 activity in the endothelium.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cellular response to resveratrol  IEP 11075079 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Serpine1  (serpin family E member 1)


Additional Information