This alteration in IRS gene expression, particularly with regard to the up-regulation of IRS-1 in SH-Sy5y cells, is reminiscent of the findings in hepatocellular carcinoma cells [63,64], and suggests that IRS protein levels may be critical for regulating robustness of insulin and IGF-1-transmitted signals, including those that stimulate AAH. Here, IGF1 is linked to hepatocellular carcinoma.