Title : Metformin inhibits TNF-alpha-induced IkappaB kinase phosphorylation, IkappaB-alpha degradation and IL-6 production in endothelial cells through PI3K-dependent AMPK phosphorylation.

Pub. Date : 2009 May 15

PMID : 18597869






6 Functional Relationships(s)
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1 Metformin inhibits TNF-alpha-induced IkappaB kinase phosphorylation, IkappaB-alpha degradation and IL-6 production in endothelial cells through PI3K-dependent AMPK phosphorylation. Metformin tumor necrosis factor Homo sapiens
2 The effects of metformin on TNF-alpha-induced IL-6 production were investigated. Metformin tumor necrosis factor Homo sapiens
3 Pre-treatment with metformin (100-1000 micromol/L) also inhibited TNF-alpha-induced IL-6 production, phosphorylation of IkappaB kinase (IKK) alpha/beta and IkappaB-alpha degradation. Metformin tumor necrosis factor Homo sapiens
4 Metformin increased phosphorylation of AMP-activated kinase (AMPK) but wortmannin, a PI3K inhibitor, negated its effects on AMPK phosphorylation and TNF-alpha-induced IkappaB-alpha degradation. Metformin tumor necrosis factor Homo sapiens
5 Transfection of siRNA against alpha1-AMPK eradicated the inhibitory effects of metformin on TNF-alpha-induced IL-6, implying the essential role of AMPK. Metformin tumor necrosis factor Homo sapiens
6 CONCLUSIONS: Metformin had anti-inflammatory effects on endothelial cells and inhibited TNF-alpha-induced IKKalpha/beta phosphorylation, IkappaB-alpha degradation and IL-6 production in HUVEC. Metformin tumor necrosis factor Homo sapiens