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,
short-chain 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.