VEGFD and hepatocellular carcinoma: In this study, we found that amino acid deprivation upregulated IRS2 transcription and translation in rat primary hepatocytes and HuH-7 hepatoma cells and that this increased expression of IRS-2 promoted the secretion of growth factors and cytokines, such as vascular endothelial growth factor-D (VEGF-D), in an insulin-independent manner via a novel mechanism.