Search

Background/aim: Animal experiments have shown that vagal cholinergic stimulation causes an increase in proximal gastric tone, but little is known about the effect of vagal stimulation on proximal gastric motor function in humans. Vagal cholinergic stimulation can be elicited by modified sham feeding (MSF) or by insulin-induced hypoglycemia. The aim of our study was to investigate the effect of MSF and insulin-induced hypoglycemia on the motor and sensory function of the proximal stomach in humans., Methods: Eight healthy volunteers participated in random order in three experiments: (A) control experiment, (B) MSF and (C) intravenous insulin injection. Intragastric volume was recorded with a barostat set at a constant preselected pressure level (MDP + 2 mm Hg). Pancreatic polypeptide (PP) secretion was measured as an indicator of cholinergic tone., Results: PP secretion increased significantly after both MSF (p<0.05) and insulin administration (p<0.01). No changes in intragastric volume were seen after MSF, while intragastric volume increased significantly in response to insulin-induced hypoglycemia when compared to control (290+/-43 vs. 148+/-24 ml; p<0.01). No differences in perception scores were seen between the three experiments., Conclusions: Vagal cholinergic stimulation by MSF has no effect on the motor function of the proximal stomach, while insulin-induced hypoglycemia causes a relaxation of the proximal stomach., (Copyright 2000 S. Karger AG, Basel.)

Background/aims: It has been suggested that the distal portion of the dorsal pancreatic duct and the ventral pancreatic duct usually merge into the main pancreatic duct, and the proximal portion of the dorsal pancreatic duct becomes the accessory pancreatic duct. In this study, we investigated the embryology of the accessory pancreatic duct roentgenographically and immunohistochemically., Methods/results: The accessory pancreatic duct shows two different patterns in pancreatograms: the long and the short type. The accessory pancreatic duct of the long type forms a straight line and joins the main pancreatic duct at the neck portion of the pancreas. The accessory pancreatic duct of the short type joins the main pancreatic duct near its first inferior branch. Long inferior branches from the accessory pancreatic duct were found in 74.6% with the long type, significantly more often than in the short type (29. 3%). Patency of the long type was (74.5%) significantly greater than in the short type (36.2%). Immunohistochemically, we found the main pancreatic duct between the junction with the accessory pancreatic duct and the neck portion of the autopsy pancreas in the short type was located within the ventral pancreas, characterized by pancreatic polypeptide-rich islets., Conclusion: The long type represents a continuation of the main duct of the dorsal primordium. The short type is very likely formed by the proximal main duct of the dorsal primordium and its long inferior branch, with the main duct of the dorsal primordium at the point of connection with the main duct of the ventral primordium being obliterated and replaced by this additional communication.

The purpose of this study was to determine the regulation of pancreatic polypeptide (PP) release by using pirenzepine (a specific M1 muscarinic receptor antagonist), 4-diphenylacetoxy-N-methylpiperidine methobromide (4-DAMP, a specific M3 muscarinic receptor antagonist), atropine (a nonspecific muscarinic receptor antagonist), and loxiglumide (cholecystokinin, CCK, receptor antagonist) in dogs. In conscious dogs with chronic gastric and duodenal fistulas, release of PP and exocrine pancreatic secretion were stimulated by constant intravenous infusion of CCK-8 (200 ng/kg/h). Graded doses of pirenzepine (0.18-4.7 mmol/kg/h), 4-DAMP (6.7-180 nmol/kg/h), or atropine (0.89-24 nmol/kg/h) dose-dependently reduced plasma PP responses to CCK-8 without influence on exocrine pancreatic secretion. ID50 calculated from these results were 492 +/- 150 nmol/kg/h for pirenzepine, 10.7 +/- 1.8 nmol/kg/h for 4-DAMP and 19.4 +/- 5.2 nmol/kg/h for atropine. A similar sequence in the inhibitory potency was observed in 2-deoxy-D-glucose (2-DG, 100 mg/kg)-stimulated PP release, exocrine pancreatic, and gastric secretions. On the other hand, loxiglumide, a CCK receptor antagonist, did not influence PP release stimulated by 2-DG. These findings suggest that both CCK- and 2-DG-stimulated PP releases are mainly under cholinergic nerve control mediated by M3 muscarinic receptor in dogs.

We have investigated the effect of acute stable hyperglycemia on gastric acid secretion and serum gastrin and pancreatic polypeptide (PP) release. Gastric acid output was measured under basal conditions and in response to modified sham feeding (MSF) in 7 healthy volunteers on two separate occasions: during normoglycemia (serum glucose 5 mmol/l) and during hyperglycemia (serum glucose 15 mmol/l). PP secretion was determined as an indirect measure of vagal-cholinergic tone. Basal acid output during hyperglycemia (4.7 +/- 1.0 mmol/h) was not significantly different from euglycemia (5.4 +/- 0.6 mmol/h), but MSF-stimulated acid output during hyperglycemia (14.7 +/- 3.3 mmol/90 min) was significantly (p < 0.05) reduced compared to euglycemia (24.7 +/- 3.2 mmol/90 min). Serum gastrin levels were not affected by MSF. During hyperglycemia, the integrated PP secretion in response to MSF (235 +/- 95 pmol/l.90 min) was significantly (p < 0.05) reduced compared to euglycemia (434 +/- 71 pmol/l.90 min). This study indicates that (1) serum glucose affects cephalic-stimulated gastric acid secretion, and (2) PP secretion after MSF is significantly reduced during hyperglycemia suggesting impaired vagal-cholinergic activity during hyperglycemia.

The effect of gastric distension on plasma cholecystokinin (CCK), pancreatic polypeptide (PP) and gastrin concentrations was investigated in healthy volunteers. Fundic and antral distension was achieved by balloons attached to a gastric tube and inflated with 300 and 600 ml and 100 and 200 ml of air for fundic and antral distension, respectively. Gastric juice was continuously aspirated. Fundic distension was additionally studied during a concomitant intravenous infusion of atropine (5 micrograms/kg/h) or a bolus injection of propranolol (2 mg). Fundic distension with 300 ml caused a significant increase in PP release (+17% above basal). Distension with 600 ml significantly stimulated CCK (+81%), gastrin (+31%) and PP output (+74%) over 30 min. Atropine completely blocked PP release and almost abolished CCK release, whereas gastrin output was enhanced. Propranolol did not prevent CCK release induced by fundic distension, whereas gastrin and PP responses were diminished. Antral distension did not cause any significant changes in hormone response. In conclusion, we demonstrated a gastric phase of CCK release which is atropine sensitive, but not influenced by propranolol.

Exclusion of bile and pancreatic juice (BPJ) from the proximal intestine increases the release of pancreatic polypeptide (PP) from 4.4 to 14.3 pM and its increase was diminished by the intravenous infusion of atropine (100 micrograms/kg/h) in conscious rats. Neither intravenous bolus injection nor continuous infusion of cerulein did increase plasma PP concentration. It is suggested that the increase in plasma PP concentration produced by BPJ diversion is regulated by cholinergic mechanism, but not by cholecystokinin (CCK) released despite the known fact that BPJ diversion increases plasma CCK concentration.

The effects of the selective muscarinic M1-receptor antagonist pirenzepine and the nonselective muscarinic antagonist atropine on bombesin- and peptone-stimulated release of pancreatic polypeptide (PP) were studied in healthy subjects. To exclude any effect of changes in intraduodenal pH continuous intragastric titration was performed during all tests. Both pirenzepine (i.v. bolus 0.6 mg/kg) and atropine (i.v. bolus 15 micrograms/kg, followed by an infusion of 5 micrograms/kg.h) significantly reduced peptone-induced integrated mean rise of plasma PP from 28 +/- 5 to 8 +/- 4 and -2 +/- 5 pmol/l, respectively (n = 4). Both drugs also reduced bombesin-induced rise of plasma PP in all 4 subjects, from 27 +/- 12 to 6 +/- 4 and 7 +/- 1 pmol/l (0.05 less than p less than 0.1). It is concluded that cholinergic regulation of PP release is mediated mainly through muscarinic M1-receptors.

The secretion of pancreatic polypeptide (PP) seems to be controlled by vagal cholinergic mechanisms, since both vagotomy and atropine significantly inhibit the PP response to food intake, sham feeding or insulin hypoglycaemia. In the present study, we examined the PP response to a meal after orthotopic autotransplantation of the pancreas. Completeness of vagal pancreatic denervation was confirmed by the missing response of pancreatic protein and the PP response to insulin hypoglycaemia. Total vagal denervation of the pancreas did not alter the PP response to a meal (peak PP levels 402 +/- 41 pg/ml before transplantation compared to 510 +/- 98 pg/ml after operation). The secretion of PP after food intake seems not to be mediated by direct vagal innervation of the pancreas itself. Since pancreatic autotransplantation results in an interruption of gastropancreatic or enteropancreatic neural reflexes, our results confirm the findings of Debas et al. [Surgery 92:309-313, 1982] and strongly suggest that the PP response to nutrient stimuli is mediated by a humoral mechanism.

Previous studies have shown that pancreatic polypeptide (PP) secretion is regulated by efferent, vagal stimulation. In the present study the afferent part of a vagovagal pathway has been investigated in two different ways: (I) Graded fundic distention: in 8 patients with duodenal ulcer ballon distention with 150 ml of the fundus and the body of the stomach increased PP concentrations in plasma from 19 (17--26) to 41 (35--48) pmol/l, median and interquartile range. Distention by 300 and 600 ml did not further increase PP concentrations. After denervation of the fundus by proximal gastric vagotomy, no increase in PP levels was observed during distention with 50 and 300 ml whereas distention by 600 ml was followed by a small increase. (II) Graded antral distention: balloon distention with 50, 100 and 150 ml of the antrum increased plasma PP concentrations in 7 healthy subjects and 14 duodenal ulcer patients. Maximal PP response was achieved by distention with 100 ml, healthy subjects: from 14 (12--23) to 40 (26--44) pmol/l, and duodenal ulcer patients: from 25 (13--38) to 47 (22--63) pmol/l, median and interquartile range. It is concluded that a gastropancreatic reflex stimulating PP secretion through a long vagovagal pathway is present in man, and that this mechanism probably is involved in the initial PP response during a meal.

In order to evaluate whether gastric inhibitory polypeptide (GIP) could be responsible for the postprandial fall in serum gastrin previously observed in patients with achlorhydria, 7 achlorhydric patients were given 100 ml Lipomul (66 g triglycerides) on one occasion, and 5 of these patients were later given a 30-min intravenous infusion of porcine GIP in a dose of 1 microgram/kg. Following the Lipomul ingestion, serum gastrin fell significantly, whereas no effect on serum gastrin was seen during the intravenous GIP infusion. A small, but significant release of serum insulin was seen shortly after starting the GIP infusion, together with a significant and more sustained release of plasma pancreatic polypeptide (PP). It is concluded that GIP does not lower the serum gastrin levels in achlorhydric patients, but that GIP might participate in the intestinal phase of the PP release.

A dose-response study of the effect of 0.1-5.0 micrograms kg-1 h-1 somatostatin was performed on food-induced rise of pancreatic polypeptide and insulin in 4 dogs. There was a dose-dependent suppression of the release of pancreatic polypeptide and insulin with an ED50 of approximately 0.65 and 0.8 microgram kg-1 h-1, respectively, during the first 45-min period. In the second 45-min period, high doses of somatostatin failed to suppress insulin concentrations whereas, the serum concentrations of pancreatic polypeptide were reduced by a similar degree as in the first 45 min. The differing effects of somatostatin on food-stimulated serum concentrations of insulin and pancreatic polypeptide indicate that somatostatin does not represent a uniform suppressor of pancreatic hormones.

Human pancreatic polypeptide (HPP) was infused into 6 anesthetized dogs at a constant dose of 1.0 micrograms/kg/h over 60 min. Blood samples for RIA of pancreatic polypeptide were taken repeatedly from a carotid artery, jugular vein, femoral vein, renal vein and mesenteric vein. The calculated tissue removal of HPP in a single passage through these four vascular beds ranged from 24 to 40% and did not differ significantly among them. Mean disappearance half-time on stopping the infusion was 4.5 +/- 0,8 min. The results indicate that HPP is removed at all of the capillary beds tested.

4 healthy volunteers received commercial 20% pure CCK-33 in 4 consecutive doses of 0.5, 1.0, 2.0, 4.0 IDU/kg/h. blood samples were assayed for pancreatic polypeptide (PP) by radioimmunoassay. Plasma PP concentrations increased stepwise from a basal level of 67 +/- 15 pmol/l to a maximum of 198 +/- 46 pmol/l (p less than 0.05). In 4 mongrel dogs with Thomas cannulas, the same doses of 99% pure CCK-33 were successively infused. Plasma PP concentrations rose stepwise with each dose from 44 +/- 7 to 259 +/- 43 pmol/l (p less than 0.02). This rise significantly correlated with pancreatic protein secretion (p less than 0.01). It is concluded that intravenous CCK-33 induces the release of PP in man and in dog, in a dose-dependent manner.

Lithium is a cation which has central nervous system effects and is able to interfere with both the release and action of polypeptide hormones. We examined its effect on basal and stimulated plasma gastrin and pancreatic polypeptide (PP) levels in 4 dogs with chronic gastric fistulas. Gastrin and PP release were stimulated by a meal or bombesin nonapeptide infusion (1.2 microgram kg-1h-1). The studies were repeated 24h and 14 days after lithium administration (600 mg/12 h) orally. Basal plasma lithium values were undetectable and rose to 0.9 /+- 0.2 mmol l-1 in the acute and 1.0 +/- 0.2 mmol l-1 in the chronically treated animals. The dogs did not have any discernible side effects. Basal plasma gastrin was 14 +/- 4 fmol ml -1 and was not significantly altered by either 1 or 14 days Li+( p greater than 0.05). Gastrin release stimulated by either a meal or bombesin was not significantly decreased by acute or chronic Li+ administration . Acute lithium administration produced a slight but significant increase in meal-stimulated gastrin (p less than 0.01). Neither acute nor chronic lithium administration altered bombesin stimulated gastric acid secretin (p greater than 0.05). Basal PP levels were 24 +/- 7 fmol ml-1 and not significantly altered by 1 or 14 days Li+ administration. Both acute and chronic Li+ inhibited PP release by bombesin in the first 30-min period of the study (p less than 0.01). 14 days Li+ significantly inhibited both first and second hour PP responses to a meal (p less than 0.01). The mechanism of the cationic modification of the release of pancreatic polypeptide requires further elucidation.

The direct vagal innervation of the pancreas in dogs was interrupted by extragastric vagotomy (EGV). The response of pancreatic polypeptide (PP) to a protein meal and to hypoglycemia was compared preoperatively, after EGV and after truncal vagotomy (TV). EGV had no detectable effect on PP secretion under basal or stimulated conditions. After TV, the PP response to a protein meal was reduced and totally abolished in response to insulin hypoglycemia when compared to preoperative results. This indicates that direct innervation of the pancreas is of little importance for the release of PP but that vagal innervation of the stomach is important provided that the vagal fibers to PP cells all pass through these extragastric vagal branches.

Mean fasting levels of pancreatic polypeptide (PP) in 24 patients with Zollinger-Ellison syndrome (ZES) and in 12 patients with hyperparathyroidism originating from families with multiple endocrine adenomatosis type I (MEAI-HPT) were significantly higher than in 72 normal controls. The overlap between the 3 groups, however, was large. In patients with ZES, increased PP levels were not related to the presence of MEAI or metastases; nor was there a correlation between serum PP and gastrin concentrations. The post-prandial PP release in 10 ZES patients and in 10 patients with MEAI-HPT was lower than in 9 normal controls. The physiological significance of the present findings is unclear.

Abnormal gastric motility has been recognised recently in some patients with excessive gastro-oesophageal reflux. The cause of this motility disturbance is unknown. A dual isotope study has been used to assess gastric emptying of solid and liquid components of a test meal in 16 patients with erosive oesophagitis and in 16 control subjects. The release of insulin, gastrin, pancreatic polypeptide, gastric inhibitory polypeptide and neurotensin in response to the test meal was monitored in all subjects. A significant delay in both solid and liquid emptying was observed in patients with erosive oesophagitis. However, they demonstrated no alteration in the pattern of hormone release in response to the test meal.

During modified sham feeding (MSF) the role of endogenous gastric acid secretion and the influences of the autonomic nervous system on the release of pancreatic polypeptide (PP) and gastrin have been studied in 12 healthy subjects (aged 24-38 years). Sham feeding was performed without pretreatment (control) and after pretreatment with 400 mg cimetidine, 80 mg propranolol (both given orally) or 1 mg atropine administered subcutaneously 60 min prior to sham feeding. MSF induced a significant increase (about 100%) in PP release. Its early peak was reduced by pretreatment with propranolol whereas cimetidine had no effect. Atropine completely abolished the PP response. Gastrin release was stimulated by MSF only after prior administration of cimetidine and, to a lesser extent, after atropine pretreatment. It is concluded that: (1) the PP release after stimulation is under strong cholinergic control but is also mediated--particularly in the early phase--by adrenergic mechanisms; (2) endogenously released acid during vagal stimulation plays a minor role in the modulation of PP secretion, but (3) masks gastrin response to MSF.

The present case report demonstrates the history of a 50-year-old man with a mixed endocrine-neurogenous tumor of the ampulla of Vater. The tumor was localized endoscopically after an attack of melena. There were no signs of endocrinopathy. A local resection with suturing of the pancreatic duct was performed. Morphologically, there were two different tissue types (neurogenous and carcinoid-like) with numerous cells and nerve fibers reacting immunohistochemically with somatostatin and neurotensin antisera: some immunoreactivity to PP-antibodies was observed. Still, after 20 months, the patient seems to have been cured by local resection.