Jan B. Jansen

Temporal relationships of cholecystokinin release, pancreatobiliary secretion, and gastric emptying of a mixed meal

The influence of gastric emptying of nutrients on plasma cholecystokinin and pancreatobiliary functions is poorly understood. We therefore temporally related the emptying of fat, protein, and glucose of a mixed meal to release of the gut hormones cholecystokinin, pancreatic polypeptide, and peptide YY and outputs of trypsin, lipase, bilirubin, and bile salts. Five healthy volunteers with a multilumen duodenal tube ingested a mixed meal with phase-specific markers for the aqueous phase, liquid fat, solid fat, and solid protein phases. Duodenal passage was determined by intraduodenal infusion of a second set of phase-specific nonabsorbable markers. Plasma cholecystokinin levels and pancreatobiliary secretions rose to a maximum at 30-60 min and then gradually declined (p less than 0.01) despite continued entry of protein and fat into the duodenum throughout the whole 4-h experimental period. High levels of both pancreatic polypeptide and peptide YY were observed in the last 2 h of the experiment. Release of factors capable of inhibiting cholecystokinin release and subsequently pancreatobiliary secretion may be responsible for the observed time-course.

Evidence That Gastrin 34 Is Preferentially Released from the Human Duodenum

A method for extraction and concentration of gastrin components from large volumes of plasma by affinity chromatography combined with gel filtration and radioimmunoassay with region-specific antibodies was used to measure gastrin components in plasma obtained from human subjects during fasting and 45 min after a mixed meal. In plasma from 6 normal and 6 unoperated duodenal ulcer subjects, gastrin 34 was twice as abundant as gastrin 17 during fasting but both components increased to a similar extent after the meal. Small but significant increases were found in component 1 but not in gastrin 14, but these forms comprised a minor fraction of total gastrin. The only significant difference found between normal and ulcer subjects was a lower amount of nonsul f ated gastrin 17, but not of total gastrin 17, in duodenal ulcer patients after the meal. In contrast, 6 fasting duodenal ulcer patients with previous subtotal gastrectomy and gastroduodenostomy had significantly lower concentrations of all gastrin components except gastrin 34 when compared with the unoperated ulcer patients and gastrin 34 was the only component that increased significantly after a meal. These results are compatable with a duodenal source of circulating gastrin. Calculations based on the known differences in concentra tion of extractable gastrin in antral mucosa (11 gastrin 34) and duodenal mucosa (57% gastrin 34) and an estimated 7.5-fold slower clearance rate of gastrin 34 compared with gastrin 17 in the circulation indicate that the duodenum could account for all basal gastrin in antrectomized patients and 40%–50% of basal gastrin in unoperated patients. Similar calculations indicate that up to one-third of gastrin released by a meal in unoperated subjects could originate in the duodenum.

Pancreatobiliary responses to an intragastric amino acid meal: Comparison to albumin, dextrose, and a maximal cholecystokinin stimulus

Little is known about how gastric and pancreatobiliary responses differ after intake of elemental diets from responses to polymeric food. We therefore compared pancreatic and biliary secretions after gastric instillation of albumin (7 g%, with dextrose 21 g%) with an elemental diet in 6 healthy volunteers. The elemental diet contained amino acids (7 g%, with dextrose 21 g%) in the same molar composition as the albumin. Furthermore, we studied the effect of a pure intragastric dextrose solution (21 g%) on pancreatobiliary secretions, as glucose constitutes a major component of elemental diet formulas. The various pancreatobiliary responses were tested against a maximal i.v. cholecystokinin stimulus. The dextrose, amino acid, and albumin meals emptied at similar rates, and gastric emptying was completed within 3 h. Similar pancreatobiliary responses were observed after the albumin and amino acid meals, but response to both the amino acid and albumin meals was smaller than to the intravenous cholecystokinin stimulus. The glucose meal caused a marked and sustained stimulation of pancreatobiliary outputs, which did not differ significantly from the other test meals. However, lower cholecystokinin levels were observed after the glucose meal compared with distinct cholecystokinin release after the albumin and amino acid meals. We conclude first that there are no major differences in secretory responses between elemental (amino acid) and polymeric (protein) meals and second, that intragastric pure glucose meals strongly stimulate pancreatobiliary secretions. The marked pancreatic and biliary responses to intragastric dextrose cannot be fully explained on the basis of cholecystokinin release, suggesting that this response is probably mediated by neural mechanisms.

Effect of cisapride on gallbladder motility after extracorporeal shock-wave lithotripsy

BACKGROUND/AIMS Altered gallbladder motility is regarded as one of the important factors involved in the formation and recurrence of gallstones. Previous studies have suggested that cisapride increases postprandial gallbladder contraction and may therefore be theoretically useful in preventing stone recurrence. The aim of our study was therefore to investigate the effect of cisapride on gallbladder motility in stone-free patients after extracorporeal shock-wave lithotripsy, as compared to healthy volunteers pair-matched for age and sex. METHODS Each subject received cisapride or placebo in a double-blind, cross-over, random order. Gallbladder volumes were measured by ultrasonography in the fasting state and after intake of a standard liquid meal. Plasma cholecystokinin levels were determined by radioimmunoassay. RESULTS Fasting gallbladder volumes were smaller in patients as compared to volunteers (20.7 +/- 1.3 ml vs. 46.0 +/- 9.2 ml; p < 0.05) but were not modified by cisapride (21.1 +/- 1.7 ml vs. 58.6 +/- 11.3 ml). The maximal postprandial decrease in gallbladder volume was similar in patients and volunteers (64.5 +/- 12% vs. 62 +/- 10%; NS) and was not significantly altered by cisapride (59 +/- 9.4% vs. 54 +/- 9%; NS). In patients, cisapride increased integrated postprandial gallbladder volume by accelerating gallbladder refilling as compared to placebo by 37 +/- 15% (p < 0.05). Integrated cholecystokinin plasma levels were similar in patients and volunteers and were 13.4 +/- 4.7% higher after cisapride as compared to placebo (p < 0.05). CONCLUSIONS The results of this study suggest that cisapride does not alter postprandial gallbladder contraction but accelerates gallbladder refilling in patients free from gallstones after extracorporeal shock-wave lithotripsy. This effect of cisapride is probably due to an acceleration of gastric emptying also causing a secondary enhanced cholecystokinin release.

Diagnostic efficacy of the secretin stimulation test for the Zollinger-Ellison syndrome: an intra-individual comparison using different dosages in patients and controls.

Background/Aims: The secretin stimulation test is the principal diagnostic tool to identify Zollinger-Ellison syndrome (ZES). We investigated, by intra-individual comparison, which dose of secretin results in the highest diagnostic efficacy to identify the ZES. Methods: Fifty-seven paired secretin stimulation tests, using both 0.26 µg/kg and 0.78 µg/kg secretin, performed in 13 ZES patients and 12 controls, were analyzed and the findings confirmed in a validation cohort. Results: A gastrin increase of >100 ng/l was found to be the most sensitive and specific criterion for a positive test. Higher gastrin increases after 0.78 µg/kg compared to 0.26 µg/kg secretin contributed to a slightly more sensitive (82.9 vs. 80.5%) but less specific (68.8 vs. 81.3%) test. A validation cohort, with 98 tests using 0.26 µg/kg secretin in 21 ZES patients and 39 controls, provided similar results. In ZES patients with normal fasting serum gastrin levels (<100 ng/l), there was no diagnostic benefit from the use of a higher secretin dose. Conclusions: The 0.26 µg/kg secretin stimulation test has the best diagnostic efficacy for the ZES.