AKT1 and cholestasis: Using the IPRL model, which unlike IRHCs allow for the dissection of mechanisms occurring separately in time, we had shown a differential role for cPKC and PI3K in E217G-induced cholestasis: whereas cPKC is involved in the initial reduction in bile flow due to transporter endocytosis, PI3K (via Akt) blocks the otherwise spontaneous reinsertion of the endocytosed transporters [9].