Indeed, Bmal1 protein amounts were significantly reduced in the nuclei but increased in the cytosol by insulin treatment in human hepatoma HepG2 cells or primary hepatocytes, as demonstrated by immunoblotting or immunostaining results (Fig. 1a,b), whereas insulin had little effect on the nucleus-cytosol shuttling of other key clock members (Clock, Cry1 and Per1, Fig. 1a). Here, INS is linked to hepatocellular carcinoma.