Furthermore, drugs used to treat T2DM, which also improve hepatic steatosis, such as rosiglitazone and metformin, are found to preferentially increase and restore IRS-2 expression. The main finding of this report is that the amount of circulating insulin is a major modulator of hepatic steatosis via regulation of liver fatty acid transport proteins. In both in vitro and in vivo experiments, insulin-mediated TG accumulation in the liver exhibited a bimodal function, where both hypo and hyperinsulinemia led to augmented liver fat storage. While we observed FG-4592 reduced FATP 2 and 5 in these experiments, the reduction in TG levels could also be attributable to enhanced fatty acid oxidation, decreased de novo lipogenesis or altered lipoprotein export. These pathways definitely need to be evaluated in future experiments in order to understand the contribution of altered FFA uptake. Ultimately, the sums of all of these processes appear to be mediated via an imbalance of insulin substrates, where hypoinsulinemia is characterized by excessive IRS-2 signaling, and hyperinsulinemia with predominant IRS-1 signaling. Regardless as to which side the equilibrium is shifted; imbalanced insulin signaling points to a common potential FATP response. The identification and verification of this novel link in follow up experiments may provide future therapeutic targets for the treatment of obesity associated fatty liver disease. The androgen receptor is a critical regulator of prostate cancer progression and it is increasingly clear that the AR is regulated not only by its cognate steroid hormone, but also by interactions with a constellation of co-regulatory and signaling molecules. For patients presenting with disseminated prostate cancer, the tumor is typically dependent on androgen for growth and therefore, initially responsive to surgical and/or pharmacological depletion of circulating androgens. However, therapeutic success is temporary. The cancer almost invariably recurs and progresses to a metastatic and lethal disease. The extensive cross talk between signaling pathways, such as androgen and peptide signaling pathways, multiple genetic mutations, and the genetic plasticity of cancer, all contribute to the inherent and acquired resistance to androgen ablation. Previous studies have demonstrated that polypeptide growth factor signal transduction pathways can stimulate AR activation, suggesting that the increase in growth factor and receptor expression could be causal in prostate cancer progression to castration resistance. Growth factor stimulation has been reported to render AR-responsive promoters hypersensitive to androgen, and forced over expression of HER2/neu in androgendependent prostate cancer cells has been shown to drive castration-resistant growth. Moreover, inhibition of EGFR/HER2 signaling can inhibit prostate cancer cell growth in vitro and in vivo as well as AR transcriptional activity, protein stability, DNA binding, and Ser 81 phosphorylation.