Peptide YY(1-36) and Peptide YY(3-36): Part I. Distribution, Release and Actions

Peptide YY (PYY) is a 36 amino acid, straight chain polypeptide, which is co-localized with GLP-1 in the L-type endocrine cells of the GI mucosa. PYY shares structural homology with neuropeptide Y (NPY) and pancreatic polypeptide (PP), and together form the Neuropeptide Y Family of Peptides, which is also called the Pancreatic Polypeptide-Fold Family of Peptides. PYY release is stimulated by intraluminal nutrients, including glucose, bile salts, lipids, shortchain fatty acids and amino acids. Regulatory peptides such as cholecystokinin (CCK), vasoactive intestinal polypeptide (VIP), gastrin and GLP-1 modulate PYY release. The proximal GI tract may also participate in the regulation of PYY release through vagal fibers. After release, dipeptidyl peptidase IV (DPP-IV; CD 26) cleaves the N-terminal tyrosine-proline residues forming PYY(3-36). PYY(1-36) represents about 60% and PYY(3-36) 40% of circulating PYY. PYY acts through Y-receptor subtypes: Y1, Y2, Y4 and Y5 in humans. PYY(1-36) shows high affinity to all four receptors while PYY(3-36) is a specific Y2 agonist. PYY inhibits many GI functions, including gastric acid secretion, gastric emptying, small bowel and colonic chloride secretion, mouth to cecum transit time, pancreatic exocrine secretion and pancreatic insulin secretion. PYY also promotes postprandial naturesis and elevates systolic and diastolic blood pressure. PYY(1-36) and PYY(3-36) cross the blood-brain barrier and participate in appetite and weight control regulation. PYY(1-36) acting through Y1- and Y5-receptors increases appetite and stimulates weight gain. PYY(3-36) acting through Y2-receptors on NPY-containing cells in the arcuate nucleus inhibits NPY release and, thereby, decreases appetite and promotes weight loss. PYY may play a primary role in the appetite suppression and weight loss observed after bariatric operations.