CANDIDATE GI HORMONES PANCREATIC POLYPEPTIDE • Pancreatic Polypeptide (PP) is a linear peptide with 36 amino acids.

• It is produced by both pancreatic islet cells and endocrine cells scattered throughout the exocrine pancreas. • The physiologic stimuli and release mechanism are not clearly identified. Protein digestion products, particularly phenylalanine and tryptophan, in the lumen of the gut are the most potent releasers; fat and carbohydrate are less effective. • PP also is released by vagal stimulation and acetylcholine. • Whether PP release is mediated by a reflex or by a hormonal mechanism is unclear. • CCK is a possible candidate for the latter role. • Current evidence suggests a role for both types of mechanism. • The primary physiologic role proposed for PP is modulating pancreatic secretion. • In physiologic doses it inhibits both basal and hormone-stimulated pancreatic secretion, having about equipotent effects on enzyme and bicarbonate secretion. • The observation that the maximum pancreatic secretory rates obtained with exogenous stimuli are not seen in response to food ingestion could be explained by PP's inhibitory effects. • Another observation that suggests PP regulates pancreatic secretion by negative feedback is that intraduodenal infusion of pancreaticobiliary juice induces PP release. • A major problem in studying this candidate hormone is that the peptide source and the target tissue are in the same organ. • This makes it difficult to clearly identify the effects of experimental maneuvers, such as denervation, on the two elements of the system. MOTILIN • Motilin is a 22-amino acid peptide found primarily in the duodenum, with lesser amounts occurring in the more distal portions of the small bowel. • Its circulating half-life is about 4.5 minutes, and the kidney appears to play an important role in its catabolism. • The physiologic stimuli for its release are not known. • Its proposed physiologic action is to initiate the migrating motor complex (MMC). • MMC is a wave of intense propulsive motor activity that sweeps the length of the gut, from stomach to ileocecal junction, at about 90-minute intervals during the interdigestive (fasting) phase of GI activity. • Plasma motilin is low during the digestive (fed) phase, but its concentration varies cyclically during the interdigestive phase and its Vytheeshwaran Vedagiri, Biochemistry For U, Chennai

peak concentration coincides with the initiation of the MMC in the stomach. ENTEROGLUCAGON • Enteroglucagon is secreted by intestinal mucosal cells, with the highest concentrations occurring in the distal small bowel and colon. • Pancreatic glucagon is a 29-amino acid peptide secreted by the alpha cells of the pancreas. • Enteroglucagon is a larger molecule. • It has 37 amino acids and differs from pancreatic glucagon in having a Cterminal octapeptide extension. • A possible hormonal role is suggested by the observation that it is released following ingestion of a mixed meal. • Intraluminal glucose and fat cause its release, with glucose being the more potent stimulus. • It has the same metabolic effects as pancreatic glucagon, i.e., stimulation of glycogenolysis and gluconeogenesis, lipolysis, and ketogenesis, but it is much less potent than the pancreatic form. • Neither pancreatic glucagon nor enteroglucagon have been clearly demonstrated to have physiologic effects on GI function. • It may play a role in inhibiting gastrin release and gastric acid secretion and in regulating intestinal cell turnover, but a physiologic role for these actions has not been established.

Vytheeshwaran Vedagiri, Biochemistry For U, Chennai

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