Pancreatic polypeptide: a unique model for vagal control of endocrine systems

Pancreatic polypeptide (PP) is a hormone synthesized only in the duodenal pancreas where the PP cell is the dominating endocrine cell type. The secretion of PP is regulated by food-intake and by plasma glucose--in both cases through vagal cholinergic mechanisms. In vitro cholinergic stimulation is 4-10 times as potent as any other stimulatory mechanism, e.g. beta-adrenergic stimulation. Although other agents such as gastrointestinal hormones and neuropeptides are potent stimulators of PP secretion in vivo, their action is totally eliminated by blockade of the muscarinic receptor and in several cases also abolished by vagotomy. Furthermore, these peptides have no or only a weak effect in vitro. The stimulation of PP secretion by hypoglycemia and inhibition by hyperglycemia is mediated also through an efferent vagal mechanism. Under extreme hypoglycemia the stimulation of PP release becomes partially atropine resistant, although still totally dependent on the vagus; conceivably the release of other transmitters, like e.g. VIP, is activated under these circumstances. In the basal state, PP secretion is under oscillating cholinergic tone. Thus, the secretion of PP is unique in the way that the cholinergic, vagal stimulation is not only the most powerful stimulatory mechanism, but also the key through which other mechanisms act. PP secretion can be used, e.g. as a sensitive indicator of autonomic disorders in patients with diabetes.