The insulin-mimetic ability of Cu2+ and Zn2+ to activate the PI3K/Akt pathway by the interaction with insulin-receptor (IR) and IGF1-receptor (IGF1R) in HepG2 human hepatoma cells (Walter et al., 2006), which result in the phosphorylation and nuclear exclusion of transcription factor FoxO1a, has been recently questioned (Hamann et al., 2014). This evidence concerns the gene INSR and hepatocellular carcinoma.