Concerning the direct effect of NOX4 on hepatocyte insulin sensitivity, an interesting study reported that siRNA-mediated knock-down of NOX4 in McArdle rat hepatoma cells in vitro resulted in selective insulin resistance with diminished insulin effects on lipid and glucose elimination but with concomitant preservation of the lipogenic and MAPK-mediated pathways [267]. Here, INS is linked to hepatocellular carcinoma.