Figure 4.

PE signaling pathway in neurons and pancreatic beta cells. PE is present in the general circulation, being secreted by several cells, such as adipocytes, skeletal muscle and the intestinal epithelium. PE is a specific K₂P TREK-1 channel blocker, thus inducing partial plasma membrane depolarization. The subsequently induced calcium entry activates several signaling pathways: Akt, ERK and CaM-Kinases. The final resulting activation upregulates CREB transcriptional activity, maintaining cellular functions. As described, secreted peptides can modulate central and peripheral targets and provide co-benefits for different but related pathologies. In both cases, the target is a common molecular system that generates similar protective and functional improvements for the challenged organs.