F. Stadil

Vagal, Cholinergic Regulation of Pancreatic Polypeptide Secretion

THE EFFECT OF EFFERENT, PARASYMPATHETIC STIMULATION UPON PANCREATIC POLYPEPTIDE (PP) SECRETION WAS STUDIED IN THREE WAYS: (a) Plasma PP concentrations increased in response to insulin-induced hypoglycemia in both normal subjects, from 11 pM (9.5-12.5) to 136 pM (118-147), n = 8 (median and interquartile range) and in duodenal ulcer patients, from 33 pM (21-52) to 213 pM (157-233), n = 7. The PP response to hypoglycemia was diminished by atropine in normal subjects (P < 0.005) and completely abolished by vagotomy in the duodenal ulcer patients. (b) Electrical stimulation, 8 Hz, of the vagal nerves in anesthetized pigs induced an increase in portal PP concentrations within 30 s from 32 pM (28-39) to 285 pM (248-294), n = 12. Minimal stimulatory frequency was 0.5 Hz and maximal stimulatory frequency 8-12 Hz. Atropine inhibited the PP response to electrical stimulation. Median inhibition with 0.5 mg of atropine/kg body wt was 74%, range 31-90%, n = 6. The response was eliminated by hexamethonium. Adrenergic alpha and beta blockade did not influence the release of PP in response to vagal stimulation. (c) Acetylcholine stimulated, in a dose-dependent manner, the secretion of PP from the isolated perfused porcine pancreas, half-maximal effective dose being 0.19 muM; maximal PP output in response to 5 min stimulation was 228 pmol, range 140-342 pmol, n = 5. Atropine completely abolished this response.The results of the present study together with the previously demonstrated poor PP response to food in vagotomized patients, indicate that vagal, cholinergic stimulation is a major regulator of PP secretion.

The inhibitory effect of glucagon-like peptide-1 (GLP-1) 7-36 amide on gastric acid secretion in humans depends on an intact vagal innervation.

BACKGROUND: Glucagon-like peptide-1 (GLP-1)(7-36) amide is an intestinal incretin hormone which also inhibits gastric acid secretion in humans. Its mechanism of action is unclear, but it strongly inhibits vagally induced secretion (sham feeding), suggesting that it could influence vagal activity. AIM/METHODS: The effect of intravenous GLP-1 (7-36 amide) (1 pmol/kg/min) was studied on pentagastrin induced acid secretion in otherwise healthy subjects, previously vagotomised for duodenal ulcer (n = 8) and in a group of young (n = 8) and old (n = 6) healthy volunteers. RESULTS: Pentagastrin increased acid secretion significantly in all three groups, but the plateau concentration in the vagotomised subjects was lower than in controls. Infusion of GLP-1 (7-36 amide) significantly inhibited acid secretion in the control groups (to 67 (SEM 6) and 74 (SEM 3)% of plateau concentrations in young and old controls, respectively) but had no effect in the vagotomised subjects. Differences in plasma concentrations of GLP-1 (7-36 amide), recovery of gastric marker, duodenal regurgitation, or Helicobacter pylori status could not explain the lack of effect. Blood glucose was lowered equally by GLP-1 (7-36 amide) in all subjects. CONCLUSION: The inhibitory effect of GLP-1 (7-36 amide) on acid secretion depends on intact vagal innervation of the stomach.

Synchronous oscillations in the basal secretion of pancreatic-polypeptide and gastric acid. Depression by cholinergic blockade of pancreatic-polypeptide concentrations in plasma.

The effect of cholinergic blockade on the concentrations of pancreatic-polypeptide (PP) in plasma was studied in 19 patients with duodenal ulcer (DU) and 16 control subjects. PP concentrations increased with age both in control subjects and in DU patients. In the DU patients atropine or benzilonium, an antimuscarinic agent with minimal cerebral actions, reduced PP concentrations from 47 (8-220) to 28 (7-53) pmol/liter, n = 18, median and total range. In the control subjects atropine suppressed the PP concentrations from 17 (0-257) to 11 (0-41) pmol/liter, n = 15. Cholinergic blockade had only a minor effect in 1 patient and 1 control, both with high PP concentrations. Both in the DU patients and in the control group the suppression by the cholinergic blockade was most marked in subjects with elevated PP concentrations. Spontaneous acid and PP secretion were measured simultaneously in 25 DU patients. No correlation was found between median acid secretion and median concentrations of PP. However, in the individual patient a positive covariation was found between fluctuations in spontaneous acid secretion and fluctuations in PP concentration. P less than 0.005. We conclude that plasma concentrations of PP in the basal state are suppressible by cholinergic blockade and that PP concentrations fluctuate synchronously with the spontaneous secretion of gastric acid. These results suggest that PP concentrations in plasma before and after cholinergic blockade may possibly serve as indicator of abdominal vagal tone.

Circulating glucagon after total pancreatectomy in man

SummaryIn five totally pancreatectomized human subjects the secretion of gut-derived glucagons was stimulated by ingestion of a meal rich in fat and carbohydrates. Glucagon-like immunoreactivity in plasma, measured with an antiserum against the 6–15 sequence, increased fivefold in response to the meal. Glucagon like immunoreactivity measured with an antiserum against the C-terminal sequence was initially normal (12–13 pmol/l), increased slightly (to 20 pmol/l), and then decreased (to approximately 6 pmol/1). The Chromatographic profile of glucagon-like immunoreactivity in plasma at maximum stimulation was studied after concentration by affinity chromatography. Both assay systems identified two peaks (at Kd-values of 0.30 and 0.60–0.65, and 0.30 and 0.70, respectively). The position at Kd 0.70 corresponds to that of glucagon 1–29. The same components may be identified in plasma from normal subjects. It is concluded that the human intestine is capable of generating all of the molecular forms of glucagon which normally are present in plasma.

Treatment of Zollinger–Ellison Syndrome with Streptozotocin

ALTHOUGH streptozotocin has been used successfully in treatment of malignant insulinomas and carcinoid tumors of the gastrointestinal tract,1 gastrinomas have apparently not been treated with this ...

Preparation of 125I-(Tyr 3)- and 125I-(Tyr 11)- neurotensin for radioimmunoassay.

The chloramine-T method for radioiodination of neurotensin for radioimmunoassay was studied. As conventional procedures produced heterogeneous preparations, labelling was performed with a low amount of chloramine-T (1.8 nmol) in the presence of excess of peptide (6 nmol). Purification and complete separation of labelled from unlabelled peptide was obtained by ion-exchange chromatography on SP Sephadex C-25. Four labelled components were identified by isoelectric focusing, enzymatic cleavage and studies of immunoreactivity. The two components representing monoiodinated preparations labelled at Tyr 3 or Tyr 11 could be isolated. Depending on the binding site of the particular antiserum the appropriate tracer could be selected for use in the radioimmunoassay. The specific radioactivities were high (2303 (2137-2407) microCi/nmol and 1927 (1608-2307) microCi/nmol (median and range] and the stability of the label and the reproducibility of the procedure was good.

Interaction of Calcium and Magnesium on Gastric Acid Secretion and Serum Gastrin Concentration in Man

The effect of magnesium on calcium- and pentagastrin-induced gastric acid secretion and on calcium-induced gastrin secretion were studied in healthy volunteers. Intravenous infusion of calcium gluconate increased serum gastrin concentration as well as gastric volume secretion, acidity, and acid output. Addition of magnesium sulfate to the infusion caused a slight but insignificant increase in serum gastrin concentration, whereas volume secretion, acidity, and acid output were significantly depressed. Intravenous infusion of magnesium sulfate had no effect on gastric acid secretion induced by a submaximal pentagastrin infusion. The results indicate that magnesium antagonizes the activation of gastric acid secretion by calcium without suppressing gastrin release and may suggest that magnesium does not change the sensitivity of the parietal cell to gastrin.

The effect of calcium on gastric acid and gastrin secretion in antrectomized subjects

Serum gastrin concentrations and gastric acid secretion were measured in nine antrectomized subjects during infusion of saline and calcium gluconate. The basal gastrin level was of the same magnitude as in normal individuals and unoperated duodenal ulcer patients. Calcium infusion only induced gastrin release in one patient and did not induce acid secretion in any of the patients.

Fasting and Meal-Stimulated Plasma Levels of Neurotensin in Obese Patients after Jejunoileal Bypass with 3:l or 1:3 Jejunoileal Ratio

The functional role of the jejunum and ileum with regard to peripheral plasma levels of intact neurotensin and NH2-terminal immunoreactivity of neurotensin was studied by using jejunoileal bypass as a model. Plasma levels were measured by radioimmunoassay before and after jejunoileal bypass randomized to different jejunoileal ratios. Seven patients were studied before bypass surgery and 28 were examined after end-to-side jejunoileal bypass with 50 cm intestine in continuity and a 3:1 or 1:3 ratio between the length of the jejunal and ileal segments. Fasting levels of intact neurotensin were unchanged by surgery, whereas levels of NH2-terminal immunoreactivity were higher in bypass patients with a long ileal segment (37.5 cm) than in unoperated patients and in those with a short ileal segment (12.5 cm). Meal-stimulated levels of intact neurotensin were higher after 1:3 than 3:1 jejunoileal bypass. The levels of NH2-terminal immunoreactivity in patients with a short ileal segment and in controls were lower than in patients with a long ileal segment. The results show that postprandial levels of both intact neurotensin and NH2-terminal immunoreactivity are related to the length of the functioning ileum and that even a difference in length of 25 cm is reflected in the circulating levels of neurotensin.