Isolation and biogenesis of a new peptide from pancreatic islets.

Abstract

Pancreatic polypeptide (PP) was discovered as a major peptide contaminant of insulin preparations1,2. The peptide is stored in a distinct endocrine cell type3 that is the predominating islet cell in the duodenal part of the pancreas4 and it is released in response to physiological events, including food intake5 and decrease in blood glucose6,7. Furthermore, infusions of PP mimicking physiological fluctuations in plasma concentrations of the peptide affect gastrointestinal functions, by inhibiting exocrine pancreatic secretion8–10 and relaxing the gallbladder10,11. Although the PP cell is more sensitive to small reductions in blood glucose than is the glucagon cell6, many studies have failed to demonstrate any metabolic effect of PP12,13. it is recognized that the biogenesis of secretory peptides by conversion of larger precursors results in multiple peptide fragments of which more than one might be bioactive14–16. Recently we identified a precursor of PP with a molecular weight (Mr) of 8,000–10,000 and showed, by pulse-chase experiments and peptide mapping, that this biosynthetically labelled precursor was converted into a low molecular weight peptide in addition to PP17. We report here the isolation and primary structure of this icosapeptide and show how it arises through an intermediate form by post-translational modification of the COOH-terminal part of the PP precursor. This second product of pro-pancreatic polypeptide conversion might fulfill the physiological potential of the major endocrine cell type of the duodenal pancreas.