However, in addition to these—perhaps not unexpected—effects of insulin on gene expression, the list of top 10 genes downregulated by insulin treatment revealed decreased expression of Tff3, Gpnmb, Soat1 and Spp1. Expression of these four genes were all increased in the NASH-STZ- hamster and increased expression of these genes has been implicated in progressive liver disease such as fibrosis and hepatocellular carcinoma [75–83], which further indicates a beneficial effect of insulin treatment on progressive liver disease. This evidence concerns the gene SPP1 and hepatocellular carcinoma.