EXPRESSION OF PEPTIDE YY IN ALL 4 ISLET-CELL TYPES IN THE DEVELOPING MOUSE PANCREAS SUGGESTS A COMMON PEPTIDE YY-PRODUCING PROGENITOR

The islets of Langerhans contain four distinct endocrine cell types pr oducing the hormones glucagon, insulin, somatostatin and pancreatic po lypeptide. These cell lineages are thought to arise from a common, mul tipotential progenitor cell whose identity has not been well establish ed. The pancreatic and intestinal hormone, peptide YY, has been previo usly identified in glucagon-producing cells in islets; however, transg enic mice expressing Simian Virus 40 large T antigen under the control of the peptide YY gene expressed the oncoprotein in beta, delta and p ancreatic polypeptide cells, and occasionally developed insulinomas, s uggesting relationships between peptide YY-producing cells and several islet cell lineages. The four established pancreatic islet cell types were examined for coexpression of peptide YY in islets of normal and transgenic mice throughout development. Peptide YY immunoreactivity wa s identified in the earliest endocrine cells in the fetal pancreas and was coexpressed in each islet cell type during development. Peptide Y Y showed a high degree of co-localization with glucagon- and insulin-p roducing cells in early pancreatic development, but by adulthood, pept ide YY was expressed in less than half of the alpha cells and was no l onger expressed in beta cells. Peptide YY was also coexpressed with so matostatin and pancreatic polypeptide when these cell types first appe ared, but most delta and pancreatic polypeptide cells continued to exp ress peptide YY throughout development. The use of conditions that dis tinguish peptide YY from the related peptides, pancreatic polypeptide and neuropeptide Y, as well as the ability of the peptide YY gene to d irect expression of a reporter gene in islets of transgenic mice, esta blishes expression of peptide YY in the earliest pancreatic endocrine cells. Coexpression of peptide YY in all islet cell types as they firs t emerge suggests that the four established islet cell types may arise from a common, previously unrecognized peptide YY-producing progenito r cell.