ABSTRACT
ApoC-IIIdirectly activates pro-infl ammatory and atherogenic signalingin vascular EC through PKCβ. Because PKCβ inhibits insulin action in endothelial cells and apoC-III activates PKCβ in the same cells, Kawakami et al. then examined whether apoC-III aff ects insulin signaling in vascular EC (Fig. 5). Th e results suggested that apoC-III inhibited insulin-inducedtyrosine phosphorylation of insulin receptor substrate 1 (IRS-1),decreasing phosphatidylinositol 3-kinase (PI3K)/Akt activationin human umbilical vein EC (HUVECs). Th ese eff ects ofapoC-III led to reduced endothelial nitric oxide synthase (eNOS)activation and NO release into the media. ApoC-III impaired insulin stimulationof NO production by vascular endothelium and induced endothelialdysfunction in vivo. Th is adverse eff ect of apoC-III was mediatedby its activation of PKCβ, which inhibits the IRS-1/PI3K/ Akt/eNOSpathway.
