Pancreatic polypeptide (PP), a member of the
neuropeptide Y (NPY) family of
peptides, is a
hormone secreted from the endocrine pancreas with established actions on appetite regulation. Thus, through activation of hypothalamic
neuropeptide Y4 (NPY4R or Y4) receptors PP induces satiety in animals and humans, suggesting potential anti-
obesity actions. In addition, despite being actively secreted from pancreatic islets and evidence of local
Y4 receptor expression, PP mediated effects on the endocrine pancreas have not been fully elucidated. To date, it appears that PP possesses an acute insulinostatic effect, similar to the impact of other
peptides from the NPY family. However, it is interesting that prolonged activation of pancreatic Y1 receptors leads to established benefits on beta-cell turnover, preservation of beta-cell identity and improved
insulin secretory responsiveness. This may hint towards possible similar anti-diabetic actions of sustained
Y4 receptor modulation, since the Y1 and Y4 receptors trigger comparable cell signalling pathways. In terms of exploiting the prospective therapeutic promise of PP, this is severely restricted by a short circulating half-life as is the case for many regulatory
peptide hormones. It follows that long-acting,
enzyme resistant, forms of PP will be required to determine viability of the
Y4 receptor as an anti-
obesity and -diabetes
drug target. The current review aims to refocus interest on the biology of PP and highlight opportunities for therapeutic development.