Neural regulation of pancreatic polypeptide release.

To clarify the nervous system's role in the regulation of pancreatic polypeptide (PP) release, extrinsic innervation to the in situ pancreas was eliminated in five dogs. Before and 2 weeks after denervation, PP was measured during insulin hypoglycemia and ingestion of a protein meal. Exogenous insulin caused a similar marked hypoglycemia in both control and denervated dogs. Hypoglycemia caused a significant increase in plasma PP in control dogs from a baseline of 42 +/- 8 pg/ml to 86 +/- 18 pg/ml at 20 minutes (P less than 0.01). In denervated dogs plasma PP did not increase with hypoglycemia, and levels were significantly less than in the control animals at 30 and 60 minutes (P less than 0.05). With a protein meal, PP increased in the control animals from 53 +/- 12 to 116 +/- 16 pg/ml at 10 minutes (P less than 0.05), 164 +/- 22 pg/ml at 20 minutes (P less than 0.05), and 193 +/- 20 pg/ml at 60 minutes (P less than 0.01). Denervation markedly blunted this response, and PP increased only from 53 +/- 6 to 64 +/- 4 pg/ml at 10 minutes, to 83 +/- 12 pg/ml at 20 minutes, and to 91 +/- 8 pg/ml at 60 minutes. PP became significantly elevated above baseline in denervated dogs only at 60 minutes (P less than 0.05), and PP was significantly lower than in the control group at 10, 20, and 60 minutes after the meal (P less than 0.05). Immunostaining for insulin, glucagon, somatostatin, and PP showed no difference in the number and distribution of these endocrine cells in predenervation and postdenervation specimens. Adrenergic and cholinergic nerves were seen in all control specimens but, except for a few adrenergic fibers, were not seen in denervated animals. Peptidergic nerves that contained vasoactive intestinal polypeptide (VIP) were seen in all areas of the pancreas before and after denervation. This study confirms that the initial rise in PP with a protein meal is governed by vagal cholinergic pathways. Later postprandial PP secretion is controlled by an interplay between these cholinergic pathways and other uncertain influences such as hormonal or substrate changes. The pancreas has a rich intrinsic peptidergic system of VIP-containing nerves.

[1]  J. Harmon,et al.  Role of the small intestine and gastric antrum in pancreatic polypeptide release. , 1981, The American journal of physiology.

[2]  P. Devitt,et al.  Release of pancreatic polypeptide in humans by infusion of cholecystokinin , 1980 .

[3]  B. Jaffe,et al.  Evidence for cholinergic dependence of pancreatic polypeptide release by bombesin--a possible application. , 1980, Surgery.

[4]  G. Burnstock,et al.  Peptide-containing neurones connect the two ganglionated plexuses of the enteric nervous system , 1980, Nature.

[5]  A. Fink,et al.  Release of human pancreatic polypeptide and gastrin in response to intraduodenal stimuli: a case report. , 1979, Metabolism: clinical and experimental.

[6]  T. Schwartz,et al.  Cephalic phase of pancreatic-polypeptide secretion studied by sham feeding in man. , 1979, Scandinavian journal of gastroenterology.

[7]  J. Walsh,et al.  Gastric and cephalic stimulation of human pancreatic polypeptide release. , 1978, Gastroenterology.

[8]  J. Tait,et al.  Properties of rat adrenal zona reticularis cells: preparation by gravitational sedimentation. , 1978, The Journal of endocrinology.

[9]  J. Holst,et al.  Vagal, cholinergic regulation of pancreatic polypeptide secretion. , 1978, The Journal of clinical investigation.

[10]  T. Adrian,et al.  MECHANISM OF PANCREATIC POLYPEPTIDE RELEASE IN MAN , 1977, The Lancet.

[11]  T. Adrian,et al.  Distribution and release of human pancreatic polypeptide. , 1976, Gut.

[12]  J. Rehfeld,et al.  PANCREATIC-POLYPEPTIDE RESPONSE TO FOOD IN DUODENAL-ULCER PATIENTS BEFORE AND AFTER VAGOTOMY , 1976, The Lancet.

[13]  R. Chance,et al.  A newly recognized pancreatic polypeptide; plasma levels in health and disease. , 1976, Recent progress in hormone research.

[14]  J. Kimmel,et al.  Isolation and characterization of chicken insulin. , 1968, Endocrinology.

[15]  E. Schenk,et al.  HISTOCHEMICAL METHODS FOR SEPARATE, CONSECUTIVE AND SIMULTANEOUS DEMONSTRATION OF ACETYLCHOLINESTERASE AND NOREPINEPHRINE IN CRYOSTAT SECTIONS , 1967, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.