Effect of somatostatin on meal-induced gastric secretion in duodenal ulcer patients.

The effect of somatostatin, a growth hormone releasing-inhibiting hormone (GH-RIH) on basal and meal-, pentagastrin-, or histamine-stimulated gastric acid and pepsin secretion was studied in six duodenal ulcer patients. Intravenous GH-RIH infused in graded doses ranging from 0.62 to 5.0 microgram/kg/hr produced a dose-related inhibition of pentagastrin-induced acid secretion reaching about 15% of control level at the dose of 5.0 microgram/kg/hr. Acid inhibition was paralleled by a decrease in the pepsin output and accompanied by a dose-dependent reduction in serum growth hormone and insulin levels measured by radioimmunoassay. GH-RIH used in a single dose of 2.5 microgram/kg/hr produced about 85% inhibition of acid secretion induced by a meal (measured by intragastric titration) accompanied by a significant decrease in serum gastrin and insulin levels. The effect of GH-RIH on histamine-stimulated secretion was very modest and observed only after stopping the GH-RIH infusion. Thus GH-RIH suppressed acid and pepsin secretion induced by pentagastrin and a meal, and this effect was accompanied by a suppression of serum growth hormone and gastrin levels which may contribute to the inhibition of gastric secretion observed.     

Interrelationship between gastric acidity and gastrin concentration in patients with duodenal or gastric ulcer and in healthy subjects

Although increased gastric acidity may be important in the pathogenesis of duodenal ulcer, it has a less well-defined role in the formation of gastric ulcers. The present study was undertaken to determine (1) the 24-hour intragastric pH and serum gastrin profiles of 31 patients with duodenal ulcers, eight patients with gastric ulcers, and seven healthy volunteers and (2) the effect of 600 mg of cimetidine BID on these measurements. There was considerable overlap of basal acid output values in the three groups, and mean values did not differ significantly. In response to pentagastrin, the peak acid output was significantly higher in the duodenal ulcer group than in the gastric ulcer or healthy group. There were no intergroup differences in intragastric hydrogen ion (H+) activity after meals, overnight, and over 24 hours, when all subjects received placebo. However, the pH values remained at or above 4.0 for a longer period during the night in the gastric ulcer patients than in the duodenal ulcer patients or healthy subjects. There were no intergroup differences in basal gastrin concentration, but the postprandial gastrin response after each meal was higher in the gastric ulcer group than in the other two groups. In the gastric ulcer group, cimetidine suppressed H+ activity at all times; in the duodenal ulcer and healthy groups, cimetidine suppressed H+ activity only after breakfast, overnight, and over 24 hours. Cimetidine enhanced the serum gastrin response to food to a greater extent in the ulcer patients than in the healthy subjects. In the healthy subjects, the ratio of H+ to gastrin (H+:G) was higher than in the duodenal or gastric ulcer patients but was suppressed only minimally by cimetidine, whereas cimetidine markedly suppressed the H+:G ratio in both groups of ulcer patients. Patients with a history of duodenal or gastric ulcers differed from healthy volunteers in their food-stimulated gastrin response and in their H+:G ratio when treated with cimetidine. Intergroup differences in gastrin response to food, but not in intragastric pH in response to food, suggests that defective control of or response to gastrin may be important in the pathogenesis of acid-peptic disease. Cimetidine, which was effective in H+ suppression in all subject groups, may alter the sensitivity of the parietal cells to gastrin in patients with duodenal or gastric ulcers.     

Detailed comparison of basal and food-stimulated gastric acid secretion rates and serum gastrin concentrations in duodenal ulcer patients and normal subjects.

We measured basal and peak acid outputs, food-stimulated acid secretion, and basal and food-stimulated serum gastrin concentrations in a large group of duodenal ulcer patients and normal subjects. Basal and peak acid outputs were significantly higher in ulcer patients. In contrast, acid secretion was similar in the groups when food was infused into the stomach and when sham feeding was combined with meal infusion to simulate normal eating. Meal-stimulated acid secretion, expressed as a percentage of peak acid output to correct for differences in secretory capacity, was lower in ulcer patients (P less than 0.002). Basal serum gastrin concentrations were higher in ulcer patients, which may have contributed to higher basal acid output. However, increases in serum gastrin after food were similar in the groups. Duodenal ulcer patients, as a group, have increased basal and maximal acid secretion, but the amount of acid secreted and gastrin released after eating is normal.     

pH dependence of acid secretion and gastrin release in normal and ulcer subjects.

By use of a recently described method, which estimates the rate of gastric acid secretion by measuring the rate of sodium bicarbonate infusion needed to keep intragastric pH constant, gastric acid secretion rates and changes in serum gastrin were measured in five normal subjects while gastric pH was kept at 5.5, 4.0, 3.0, or 2.5. Preliminary experiments revealed that the method did not accurately measure acid secretion at a pH lower than 2.5. Stimulation of acid secretion was produced by gastric instillation of a solution of amino acids and cornstarch. The secretion rate with the amino acid meal was highest at pH 5.5 and was 60% of that produced by a steak meal at the same pH. As the pH of the amino acid meal was decreased, there was a stepwise reduction in acid secretion so that at pH 2.5 the rate was only half as great as at pH 5.5. The amino acid meal produced increases in serum gastrin that were also less marked than those produced by a steak meal. With amino acid stimulation, serum gastrin responses were similar at pH 5.5, 4.0, and 3.0, but no increase in gastrin could be measured when the meal was maintained at pH 2.5. A group of six patients with duodenal ulcers was compared with seven normal subjects at pH 5.5 and 2.5. Ulcer patients released more gastrin and secreted more acid at each time period at both pH values. More important, the degree of inhibition at pH 2.5 was significantly less in ulcer patients. For example, during the 2nd h after stimulation acid secretion was inhibited by only 30% in ulcer patients compared with 70% in normal subjects. These findings suggest a defect in autoregulation of gastrin release and gastric acid secretion at low pH in ulcer patients which may play a role in pathogenesis of this disease.     

Effects of parenteral secretin--cholecystokinin and of duodenal acid perfusion on gastric secretion in duodenal ulcer patients.

The effect of parenteral secretin-cholecystokinin and duodenal acid perfusion on broth-stimulated gastric acid secretion was studied in 11 duodenal ulcer patients. Statistically significant inhibition occurred in both experimental conditions. The effect of secretin-cholecystokinin was more marked than the effect of duodenal acid perfusion. A poorly responsive subgroup of patients appeared to be responsible for the diminished inhibitory effect of duodenal acid perfusion. In this poorly responsive group there was a diminished duodenal volume response as well as diminished duodenal acid clearing. We conclude that there may exist a diminished release of gastrointestinal hormones such as secretin and cholecystokinin in certain duodenal ulcer patients.     

Comparison of acid secretory responsiveness to gastrin heptadecapeptide and of gastrin heptadecapeptide pharmacokinetics in duodenal ulcer patients and normal subjects.

Serum gastrin concentrations and gastric acid secretion were measured during intravenous infusion of gastrin heptadecapeptide (G-17) (0, 7, 22.1, 70, 221, and 700 pmol/kg X h) in 15 duodenal ulcer patients and 15 healthy controls. Ulcer patients developed higher serum gastrin concentrations during G-17 infusion due to nearly twofold slower clearance of gastrin (8.8 vs. 15.7 ml/kg X min; P less than 0.01). Despite slower clearance of G-17, ulcer patients had plasma elimination half-times for G-17 similar to controls (6.0 vs. 6.1 min, respectively). Thus, calculated volume of distribution for G-17 was lower in ulcer patients than controls (78.5 vs. 140.7 ml/kg; P less than 0.025). For any serum gastrin during gastrin-17 infusion, acid secretion (millimoles per hour) was higher in ulcer patients than in controls. However, when acid secretion was expressed as a percentage of peak acid output to G-17 (to correct for differences in parietal cell mass), curves relating acid secretion to serum gastrin were identical in ulcer patients and controls.     

The content of gastrin, bombesin and somatostatin in the blood and gastric juice of patients with duodenal and gastric peptic ulcer]

Ninety patients suffering from peptic ulcer and 25 healthy subjects were examined for the content of gastrin, bombesin and somatostatin in blood and gastric juice. Among patients with duodenal ulcer, 2 groups were distinguished: group I included patients in whom peptic ulcer occurred before 30 years; the majority of the patients manifested blood hypergastrinemia, a decrease of bombesin concentration and normal somatostatin concentration; gastric juice was characterized by a lowering of somatostatin concentration and unchanged gastrin concentration; group II was made up of patients who developed peptic ulcer after 30: in the majority of the patients, gastrin concentration was reduced under basal conditions, after loading it was unchanged; in part of the patients, blood somatostatin concentration was elevated, in 16 in exacerbation and in 19 in remission; in the remainder, it was unchanged. The concentration of bombesin in blood remained unchanged. In gastric juice, gastrin concentration was increased only after histamine administration, somatostatin concentration was unchanged whatever the disease stage. In patients with gastric ulcer, gastrin concentration in blood was elevated only under basal conditions, being unchanged in gastric juice irrespective of the disease stage. Meanwhile, the concentration of bombesin was lowered both under basal conditions and after insulin administration, the concentration of somatostatin was decreased both in blood and gastric juice whatever the disease stage.     

Effect of vagotomy on gastrin secretion in patients with duodenal ulcer

The basal and food-stimulated gastrin secretion after selective proximal vagotomy, selective gastric vagotomy and truncular vagotomy was found to be elevated. Hypergastrinemia increased as gastric secretion was inhibited, thus attesting to the role of acid formation inhibition in the origin of the postvagotomy increase in the hormonal secretion. However the values of the intragastral pH being equal, the blood gastrin level was higher after vagotomy as compared to that seen in unoperated peptic ulcer patients. After vagotomy coupled with antrumectomy gastrin secretion remained at the level seen in the unoperated patients, indirect evidence for increased function of extraantral G cells. Inhibition of gastric secretion is no single cause of the postvagotomy hypergastrinemia, since the latter was essentially increased in the early postoperative times and in the presence of the vagotomy-induced disorders. It is concluded that increased secretion of gastrin after vagotomy secures trophic and compensatory-adaptation processes.     

Inhibition of gastrin secretion by hypertonic solutions in patients with pernicious anaemia and duodenal ulcer

Abstract. Serum gastrin increased in patients with pernicious anaemia after a beef-meal, but decreased after an oral load of glucose, xylose or sodium chloride. 50 g of glucose and 25 or 75 g of xylose suppressed serum gastrin to appoximately 40% of basal values at 60 min and were slightly more effective than 10 g of sodium chloride.
There was no rise in beef-meal stimulated serum gastrin concentration in vagotomized patients and only a slight rise in two patients with duodenal ulcer when an oral dose of 10 g of sodium chloride was given together with the beef-meal. 25 g of xylose suppressed basal serum gastrin concentration significantly in six vagotomized patients.
Nasal administration of small amounts of vasopressin decreased basal serum gastrin significantly in all subjects examined. Further studies indicated, however, that vasopressin was only effective when pharmacological plasma concentrations were attained.
The inhibitory effects of 10 g of glucose given orally and intraduodenally were compared in six patients with pernicious anaemia. Serum gastrin concentration decreased approximately to the same extent in both experiments.
It is concluded that the inhibitory effect of glucose on gastrin secretion most likely is mediated hormonally via osmo-receptors located in the small intestine.     

Gastric pepsin and acid secretion following various operations for gastric and duodenal ulcer

In 117 cases of gastric and duodenal ulcer subjected to various types of operation, insulin- and histamine-stimulated secretion of gastric pepsin and acid was investigated at follow-up. Secretory responses of gastric pepsin to the stimulation with insulin and histamine were different from those of gastric acid. Insulin was confirmed to have a greater ability than histamine to stimulate gastric pepsin secretion. In the cases of vagotomy with pyloroplasty and those of vagotomy with hemigastrectomy, the average reduction rates of peak pepsin output were 80% and 92%, respectively, after insulin-stimulation, and 52% and 74% after histamine-stimulation. In view of gastric pepsin secretion, pylorus-preserving gastrectomy and segmental gastrectomy are more physiological than distal gastrectomy.     

The relation between functioning parietal cell and gastrin cell masses in two groups of duodenal ulcer patients.

1. Serum gastrin concentrations before and after a standardized meal were determined in twenty-eight patients with duodenal ulcer and in ten normal control subjects. 2. In response to pentagastrin, thirteen of the duodenal ulcer subjects secreted acid within the limits of normal and fifteen secreted in excess. 3. The differences in the basal serum gastrin concentrations between the three groups, normal subjects, acid "normosecretors" and hypersecretors were not statistically significant but that of the hypersecretors was suggestively low. 4. The integrated gastrin response and peak gastrin responses to meals were higher in duodenal ulcer patients with normal acid secretion than in the hyper-secretors but the values for the latter were not different from normal subjects. 5. Stabilization of intragastric pH by infusion into the antrum of sodium bicarbonate during the test meal response period did not alter these differences between the two ulcer patient groups. 6. A significant inverse correlation exists between the maximal acid output and the integrated gastrin response in both normal subjects and hypersecreting duodenal ulcer patients. 7. The evidence (a) supports the existence of an inverse relationship between the functioning parietal cell and gastrin cell masses, (b) shows the gastrin response in normosecreting ulcer subjects to be inappropriately high, and (c) suggests that excessive vagotonia exerts trophic effects upon both parietal cell mass and gastrin cell mass.     

Peptic ulcer and gastric acid secretion in patients with insulinoma

We evaluated the incidence of associated peptic ulcers and the gastric acid secretion in our 20 series of insulinoma, and obtained the following results: 1) Four out of 20 patients (20%) with insulinoma were associated with peptic ulcers. 2) Except for the maximum acid concentration, the preoperative gastric secretion tests, such as the basal acid output and maximum acid output, failed to indicate hyperacidity in those patients. And patients with a short duration of illness by insulinoma neither showed hyperacidity nor were associated with peptic ulcers. 3) A tendency of reduced gastric acid secretion and the amelioration of peptic ulcers was observed in those who underwent the extirpation of insulinoma. 4) In the most recent case received gastric analysis with continuous monitoring of blood glucose level, an increase of basal acid output was observed during the hypoglycemic period in which the blood glucose levels reduced to around 30 mg/100 ml. These results indicate that the low blood glucose level and the high gastric acid secretion produced under the condition on an empty stomach, may be important factors related to the high association rates of the peptic ulcers in patients with insulinoma.     

Motor and secretion function of stomach and duodenum, duodenogastric reflux in patients with duodenal ulcer

Gastric secretion, motor function and tonicity of the stomach and duodenum, duodenogastric reflux were studied in inpatients with two clinicopathogenetic types of duodenal ulcer: observed at young age (type 1) and in later life (type 2). The examination included pH-metry with simultaneous balloon cimography, chromogastroduodenoscopy with Kongo-red, tests for Helicobacter pylori conducted on the biopsy samples. All the patients were found to have continuous acid production. High acid production was more frequently registered in males with the disease type 1, the lowest production was in females with the disease type 2. Duration of the acid inflow into the duodenum in patients with the disease type 2 was greater than that in young subjects. Mild ulcer was associated with moderate acidity in the duodenum, in severe ulcer the acidity was very high. Males with the disease 1 and 2 and females with type 2 had hyperkinetic, hypertonic gastric motor function. In duodenal ulcer prevalent is hypertonic, hyperkinetic type of duodenal motor function being most frequent among males with the disease type 2. Duodenogastric reflux occurs more often in patients with intensive acid production associated with hypotonic, hypokinetic motor type and duodenal tone.     

Role of serum fasting gastrin in screening for hypergastrinemic syndromes in duodenal ulcer disease.

Basal serum gastrin levels were measured in 237 patients with endoscopically confirmed duodenal ulcer and were higher than normal in 16 cases. Protein meal gastrin stimulation was performed on this group of 16 patients and on a control group of 48 patients with normal basal gastrin concentrations but high rates of either ulcer recurrence or of complications (e.g., bleeding or perforation); 21 patients from the two groups were also tested for serum gastrin inhibition with secretin. Four cases (25%) of antral G-cell hyperfunction were found in the first group, plus 1 case compatible with Zollinger-Ellison syndrome (6.2%). Only 1 case (2%) of antral G-cell hyperfunction was found among the 48 controls. These results suggest the clinical utility of routine basal gastrin measurement in screening for hypergastrinemic patients with duodenal ulcer disease.     

Studies on the mechanisms of food-stimulated gastric acid secretion in normal human subjects.

Liquid test meals were infused into the stomach and acid secretion was measured by intragastric titration at pH 5.0 Acid secretion after 500 or 750-ml sodium chloride meals was two to three times higher than basal secretion rates and was equivalent to 25-30% of the peak acid output in response to histamine. Since these meals did not cause a rise in serum gastrin concentration, it is assumed that they stimulate acid secretion by causing distention of the body and fundus of the stomach. Compared with this distention stimulus, glucose meals had no effect on acid secretion and fat-inhibited acid secretion; however, both glucose and fat caused an increase in serum gastrin concentration. Amino acids caused a much greater increase in serum gastrin concentration and enhanced acid secretion above that noted with distention alone. In contrast, albumin did not enhance the serum gastrin concentration or stimulate acid secretion to a statistically significant extent. There was a close correlation between the rise in serum gastrin concentration and rate of acid secretion after different test meals when average results for each test meal were plotted. However, there was a poor correlation between acid secretion and serum gastrin concentration when the responses of the individual subjects with a given test meal were compared. Our interpretations are: (a) Distention is an important stimulant of the acid-secretory response to a meal, and this is not mediated by gastrin release. (b) Gastrin is one but probably not the only mediator of the chemical phase of acid secretion, i.e., acid secretion noted with amino acids that cannot be explained by distention. (c) Glucose and fat also release gastrin; however, with glucose the rise in serum gastrin is too small and too transient to enhance acid secretion, and fat probably releases unmeasured inhibitors that overwhelm the effect of gastrin on acid secretion. (d) Albumin is not a stimulant of acid secretion.     

Increased plasma noradrenaline and serum gastrin in patients with duodenal ulcer

Serum gastrin, serum insulin, plasma noradrenaline, plasma adrenaline, pulse rate and blood pressure were measured repeatedly during 24h in six patients with duodenal ulcer and in six control subjects. Mean serum gastrin concentration was 3-4 times higher in duodenal ulcer patients than in controls during both the day and at night. Serum insulin was the same in both groups of subjects. Overnight fasting and mean supine plasma noradrenaline as well as mean supine pulse rate were significantly higher in duodenal ulcer patients than in controls. Plasma adrenaline and arterial blood pressure were the same in patients and controls. These results suggest that sympathetic nervous activity is increased in patients with duodenal ulcer. The increased sympathetic nervous activity may mean that duodenal ulcer patients are subject to more stress than normal subjects or may be compensatory to increased vagal nervous activity presumed by some authors to be present in such patients.