The epithelium of the gastrointestinal tract contains multiple cell types, including specialized cells termed enteroendocrine cells that number less than 1% of the cell population and yet form the largest endocrine system of the body. Enteroendocrine cells synthesize, store, and release chemical transmitters that are involved in gastrointestinal motility, secretion, and absorption and in regulation of appetite. These transmitters are predominantly small polypeptides that are also found in the enteric nervous system and the central nervous system. There are more than 30 gut peptide hormone genes identified, which express more than 100 bioactive peptides. They are grouped into “families” according to their primary structure. In this section, the pancreatic polypeptide family will be discussed.
Peptide YY is one of the gut peptides that belongs to the pancreatic polypeptide family of peptides, which also includes pancreatic polypeptide and neuropeptide Y. Despite sharing structural similarities and the same 36 amino acid lengths, the gut peptides vary in their biologic functions and locations. Peptide YY, neuropeptide Y, and pancreatic polypeptide bind to a family of G-protein–linked receptors (called Y receptors). At present, five receptor subtypes have been identified.
Peptide YY is secreted from L cells in the ileum and H cells in the colon in response to an oral nutrient load.
Peptide YY levels start to rise within 15 minutes of any caloric ingestion, long before the nutrients themselves reach the distal gut, implying that other neural or hormonal mechanisms are involved in its release. The actions of peptide YY are largely inhibitory. It inhibits gastrointestinal motility, pancreatic and gastric secretion, and chloride secretion, causing a delay in intestinal transit, or the so-called ileal brake. This allows for a longer contact time between nutrients and the small intestine. Peptide YY is also believed to be involved in the regulation of food intake and satiety, acting mainly via the Y2 receptors in the hypothalamus.
Pancreatic polypeptide is secreted by specialized pancreatic islet cells and inhibits gallbladder contraction and pancreatic exocrine secretion. It may influence food intake, energy metabolism, and the expression of gastric ghrelin and hypothalamic peptides. Neuropeptide Y is a neurotransmitter predominantly found in sympathetic neuron and is the most potent known stimulant of food intake.