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J Biol Chem. 2001 Aug 17;276(33):31422-8. Epub 2001 Jun 4.

Dual action of eicosapentaenoic acid in hepatoma cells: up-regulation of metabolic action of insulin and inhibition of cell proliferation.

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Third Division, Department of Medicine, and Department of Basic Allied Medicine, Kobe University School of Medicine, Kobe, 650-0017, Japan.


Exogenous administration of eicosapentaenoic acid (EPA) improves insulin sensitivity, but its precise mechanism remains unknown. Here we show that EPA stimulates the intracellular insulin signaling pathway in hepatoma cells. Exposure of these cells to EPA caused up-regulation of several insulin-induced activities including tyrosine phosphorylation of insulin receptor substrate-1, insulin receptor substrate-1-associated phosphatidylinositol 3-kinase, and its downstream target Akt kinase activity as well as down-regulation of gluconeogenesis. In contrast, EPA decreased mitogen-activated protein kinase activity and inhibited cell proliferation. These findings raise the possibility that EPA up-regulates metabolic action of insulin and inhibits cell growth in humans.

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