Cornelis B. H. W. Lamers

Plasma cholecystokinin concentrations in patients with pancreatic insufficiency measured by sequence-specific radioimmunoassays

It has been claimed that plasma cholecystokinin (CCK) concentrations are raised in patients with pancreatic insufficiency. We have measured plasma CCK concentrations in 32 patients with pancreatic insufficiency (22 alcoholic pancreatitis and 10 cystic fibrosis) and in 30 normal subjects by radioimmunoassays using antibodies with different specificties. Antibody 1703 binds to COOH-terminal forms of CCK containing at least 14 amino acid residues and does not cross-react with gastrins. Antibody T204 binds to all CCK-peptides containing the sulfated tyrosyl region and shows low cross-reactivity with sulfated gastrins but no binding to nonsulfated gastrins. Antibody 5135 binds to all COOH-terminal CCK-peptides and shows full cross-reactivity with gastrins. In patients with pancreatic insufficiency, plasma CCK concentrations (1.2±0.1 pmol/liter, antibody 1703; 2.0±0.2 pmol/liter, antibody T204; 12.5±1.4 pmol/liter, antibody 5135) were not significantly different from those in normal subjects (1.1±0.1 pmol/liter, antibody 1703; 2.2±0.3 pmol/liter, antibody T204; 10.5±0.9 pmol/liter, antibody 5135). Furthermore, plasma CCK concentrations in patients with pancreatic insufficiency due to alcoholic pancreatitis (1.2±0.1 pmol/liter, antibody 1703; 1.9±0.2 pmol/liter, antibody T204; 14.0 ±1.9 pmol/liter, antibody 5135) were not significantly different from those in patients with cystic fibrosis (1.2±0.2 pmol/liter, antibody 1703; 2.4±0.4 pmol/liter, antibody T204, 9.1 ±1.0 pmol/liter, antibody 5135). Cross-reactivity with gastrin accounted for almost all CCK-like-immunoreactivity measured with antibody 5135. Oral ingestion of 250 ml 20% Intralipid induced similar increases in plasma CCK in six patients with pancreatic insufficiency (4.3±1.5 pmol/liter, antibody 1703; 2.9±0.6 pmol/liter, antibody T204) as in seven normal subjects (5.0±0.9 pmol/liter, antibody 1703; 4.3±0.9 pmol/liter, antibody T204). It is concluded that CCK concentrations in fasting plasma are very low, that oral fat induces significant increases in plasma CCK, and that in patients with pancreatic insufficiency plasma CCK levels are not increased.

Hypergastrinemia of antral origin in duodenal ulcer.

A case of recurrent duodenal ulcer, basal gastric hypersecretion, and hypergastrinemia of antral origin is presented. The diagnosis was suggested preoperatively by stimulation tests with secretin and food. Billroth II antrectomy led to normalization of serum gastrin within half an hour. The gastrin content of the antral mucosa was not increased, neither was antral G-cell hyperplasia demonstrable. Postoperatively the basal gastric acid output and fasting serum gastrin levels were normal, without a postprandial increase in serum gastrin concentrations. The case does not support the existence of a specific disease called antral G-cell hyperplasia.

Serum gastrin responses to bombesin and food in patients with hypergastrinemia

Serum gastrin responses to bombesin and to food wer studied in patients with hypergastrinemia. Nine unoperated patients with hypergastrinemia of antral origin (seven achlorhydria and two idiopathic G-cell hyperfunction) had significantly higher serum gastrin responses to bombesin (P<0.001) and to food (P<0.001) than eight unoperated patients with Zollinger-Ellison syndrome. Three gastrectomized Zollinger-Ellison patients showed large serum gastrin responses to bombesin, and two of them had large postprandial increases in serum gastrin. Serum gastrin in a single patient with retained excluded antrum in the duodenal stump after partial gastrectomy with Billroth II anastomosis responded to bombesin but not to food. In nonoperated patients with hypergastrinemia of antral origin, the serum gastrin responses to bombesin and to food were significantly correlated (r=0.786;P<0.02) while in unoperated Zollinger-Ellison patients no such correlation was found (r=0.095;P>0.10). It is concluded that determination of the serum gastrin response to bombesin does not provide more information than measurement of postprandial serum gastrin concentrations in the differential diagnosis of patients with basal hypergastrinemia.

Comparative study of plasma pancreatic polypeptide responses to food, secretin, and bombesin in normal subjects and in patients with chronic pancreatitis

Plasma pancreatic polypeptide (PP) responses to food, secretin (1 CU/kg, intravenous) and bombesin (60 pmol/kg/20 min intravenous) were compared in 14 normal subjects and in 17 patients with chronic pancreatitis and pancreatic insufficiency. Basal plasma PP concentrations were significantly higher in normal subjects than in patients with chronic pancreatitis, but there was considerable overlap between the groups. Ingestion of food induced significant increases in plasma PP both in normal subjects and in patients with chronic pancreatitis, whereas secretin and bombesin significantly increased plasma PP levels in normal subjects only. The PP responses to the three stimuli were significantly larger in normal subjects than in patients with chronic pancreatitis, but there was marked overlap. Calculation of the peak to basal plasma PP ratio did not result in better discrimination between the two groups. In normal subjects there were no significant correlations between the PP responses to the three stimuli, whereas in patients with chronic pancreatitis these responses were significantly correlated. Furthermore, in patients with chronic pancreatitis the PP responses to the various stimuli were significantly correlated with the basal plasma PP level.

The Effect of Somatostatin on Bombesin-Stimulated Serum Gastrin and Gastric Acid Secretion in Man

The effect of intravenous somatostatin on bombesin-stimulated serum gastrin and gastric acid secretion was studied in 5 healthy subjects. Somatostatin, 100 ng/kg/min, significantly inhibited serum gastrin and gastric acid responses to infusion of bombesin-tetradecapeptide in a dose of 2.5 ng/kg/min. Inhibition of gastrin release could not fully account for the inhibition of gastric acid secretion. Since both bombesin and somatostatin are present in the antrum of man, interrelations between these peptides might be involved in gastrin release from the antrum.

Calcitonin and secretin inhibit bombesin-stimulated serum gastrin and gastric acid secretion in man.

The effect of intravenously administered calcitonin and secretin on bombesin-stimulated serum gastrin and gastric acid secretion was studied on 7 volunteers. Secretin G.I.H. (1 C.U./kg per h) and calcitonin (0.5 I.U./kg per h) significantly (P less than 0.05) inhibited the serum gastrin and gastric acid responses to bombesin-14 (90 pmol/kg per h). Inhibition of gastrin release could not fully account for the inhibition of gastric acid secretion.

Serum Concentrations of Immunoreactive Calcitonin in Patients with Hypergastrinaemia

In order to test tthe hypothesis that chronically elevated serum gastrin levels induce hypercalcitoninaemia, we have measured serum calcitonin levels in patients with chronic hypergastrinaemia. Basal serum calcitonin concentrations were found to be elevated in 2 of 23 patients with Zollinger-Ellison syndrome, but not in 16 patients with hypergastrinaemia due to achlorhydria or a single patient with primary hypergastrinaemia of antral origin. Both Zollinger-Ellison patients with hypercalcitoninaemia (0.31 and 0.79 ng/ml) had multiple endocrine adenomatosis type 1, but no medullary carcinoma of the thyroid. The hypercalcitoninaemia in these patients does not seem to be related to multiple endocrine adenomatosis type 1, since serum calcitonin was normal in 12 normogastrinaemic patients with hyperparathyroidism from families with multiple endocrine adenomatosis type 1. We conclude that chronically elevated serum gastrin levels do not result in hypercalcitoninaemia.

Effect of medium-chain triglycerides and long-chain triglycerides on plasma pancreatic polypeptide secretion in man

Since it has been shown that stimulation of pancreatic enzyme secretion by triglycerides is dependent on the chain length of the fatty acids, we have studied whether the secretion of pancreatic polypeptide (PP) in response to triglycerides is also related to the chain length of the fatty acids. Therefore, the effect of equimolar amounts (60 mmol) of medium-chain triglycerides (MCT) and long-chain triglycerides (LCT) on plasma PP was studied in 6 normal subjects. In the control study the subjects ingested 60 ml of 0.15 mol/l saline. Ingestion of LCT resulted in significant increases in plasma PP from 33 +/- 7 to 55 +/- 7 pmol/l (P less than 0.01), whereas both MCT and saline did not significantly increase plasma PP concentrations. Similarly, the integrated plasma PP secretion after LCT (1022 +/- 392 pmol/l per 90 min) was significantly greater than that after MCT (-690 +/- 358 pmol/l per 90 min; P less than 0.001) and that after saline (-462 +/- 205 pmol/l per 90 min; P less than 0.01). It is concluded that the secretion of PP in response to triglycerides is dependent on the chain length of the fatty acids.

Cholinergic regulation of pancreatic polypeptide secretion in chronic renal failure.

Secretion of pancreatic polypeptide (PP) is regulated mainly by cholinergic mechanisms and we have studied this in patients with chronic renal failure (CRF). Basal serum PP concentrations in 25 patients with CRF (401 ± 80; 116–2100 pmol/1; mean ± SEM and range) were significantly higher than in 65 normal subjects (33 ± 2; 21–120 pmol/1, P<0·001). Ingestion of a standard test meal induced significantly larger increases in serum PP in 11 patients with CRF (304 ± 45; 155–640 pmol/1) than in 11 normal subjects (140 ± 33; 51–440 pmol/1, P < 0·005). Insulin‐hypoglycaemia (0·1 U/kg i.v.) provoked similar increases in serum PP in five patients with CRF (404 ± 79; 170–665 pmol/1) as in five normal subjects (449 ± 92; 180–706 pmol/1). Administration of atropine (1 mg i.v.) did not normalize the elevated basal serum PP concentrations in five patients with CRF. On the other hand, administration of the same dose of atropine 60 min after ingestion of food decreased postprandial serum PP levels to basal values within one hour both in five patients with CRF and in six normal subjects. Sephadex G‐50 column chromatography of basal, postprandial and post‐atro‐pine sera from three patients with CRF revealed at least three different molecular forms. The PP peak coeluting with the 4200 molecular weight human PP standard comprised more than half of total PP immunoreactivity and was the only peak to be influenced by feeding or atropine. We conclude that in patients with CRF, PP secretion stimulated by cholinergic mechanisms is normal. In such patients post‐prandially released PP is dependent mainly upon cholinergic mechanisms, whereas the elevated basal serum PP concentration is not under cholinergic control.