Gastric and gallbladder emptying in relation to the secretion of cholecystokinin after a meal in late pregnancy

Gastric and gallbladder emptying was studied in response to a mixed liquid meal in 18 pregnant women and 24 controls without a history of gallbladder or liver disease. Gallbladder and gastric volumes were measured with ultrasound and calculated by the 'sum-of-cylinders' method. The gastric emptying of protein was estimated by nasogastric aspiration in separate groups of controls and pregnant women. In a subgroup of 9 pregnant women and 8 controls, the secretion of cholecystokinin (CCK) was also measured. Neither gastric volume reduction and emptying nor contraction of the gallbladder and CCK secretion after a liquid mixed meal differed significantly between pregnant women and controls. The gallbladder fasting volume and the residual volume after contraction, however, were significantly increased in pregnant women.     

Fasting gallbladder volume, postprandial emptying and cholecystokinin release in gallstone patients and normal subjects

Since abnormal gallbladder emptying may be a contributing factor in the development of gallstone disease, we determined fasting gallbladder volume and postprandial contraction in 20 gallstone patients and 20 normal subjects with the aid of ultrasonography. Moreover, basal plasma cholecystokinin levels and postprandial cholecystokinin (CCK) release were determined. Gallstone patients were divided into strong contractors (13 pts) and weak contractors (below 95% confidence interval for AUC contraction in % during 90 min: 7 pts). Strong contractor patients had significantly larger mean fasting volumes than normal subjects (mean +/- S.E.: 34.9 +/- 6.1 ml and 18.9 +/- 1.6 ml, respectively). This was not true for weak contractor patients (mean fasting volume 23.2 +/- 3.2 ml). Both strong contractor and weak contractor patients had significantly higher mean residual volumes than normal subjects (17.0 +/- 4.1 ml, 18.0 +/- 2.9 ml, and 8.8 +/- 1.1 ml, respectively). Absolute gallbladder emptying was significantly higher for strong contractor patients than for normal subjects, but relative emptying was the same. Opposite patterns of CCK release occurred in gallstone patients and normal subjects. In normal subjects, more CCK release was associated with stronger gallbladder emptying. In contrast, weak contractor gallstone patients had significantly higher CCK release than strong contractor patients. (AUC CCK: 304 +/- 89 pmol/l x 90 min and 106 +/- 29 pmol/l x 90 min, respectively). The present study indicates that strong contractor gallstone patients may have large residual gallbladder volumes due to large starting volumes, whereas weak contractor patients may have large residual volumes due to impaired contraction. Subjects with large fasting and residual volumes may be at increased risk for gallstone disease.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of Age and Gender on Fat-Induced Gallbladder Contraction and Gastric Emptying of a Caloric Liquid Meal: A Sonographic Study

In this study, the gastric emptying of a liquid fatty meal and the consecutive gallbladder contraction were simultaneously measured by ultrasound in four different age- and sex-related groups of normal subjects: group A, 15 women less than 50 yr (premenopausal); group B, 15 women greater than 50 yr (postmenopausal); group C, 15 men less than 50 yr; and group D, 15 men greater than 50 yr. Apart from a significantly delayed gastric emptying in the premenopausal women, no significant differences in the postprandial relative gallbladder emptying rates were observed between the four study groups. Ninety-five percent of all study subjects had a gallbladder volume reduction of more than 50% after a liquid fatty meal. It is therefore concluded, that 1) endogenous or contraceptive female sex hormones may have a delaying effect on gastric emptying of caloric liquids in the premenopausal state, 2) aging or gender do not significantly influence the fat-induced gallbladder contraction in man, and 3) a 50% residual volume of the gallbladder after a fatty meal should be considered as the upper limit of normal gallbladder contractility (95 percentile of a normal collective).     

Oral administration of loxiglumide (CCK antagonist) inhibits postprandial gallbladder contraction without affecting gastric emptying

The effect of a single oral dose of loxiglumide, a cholecystokinin antagonist, on postprandial gallbladder contraction and on gastric emptying was evaluated in humans. Following a 12-hr fasting period, two tablets of loxiglumide (400 mg each) or placebo was administered on different days, in random order and in a double-blind fashion to 10 healthy volunteers 15 min before the ingestion of a 1050-kcal standard meal. Gallbladder and antral volumes were measured by real-time ultrasonography in basal conditions and at fixed time intervals after the meal. Oral loxiglumide administration was followed by a total inhibition of the gallbladder contraction for 60 min after the end of the meal ingestion. Thereafter, up to the end of the study period, gallbladder volume was larger than that of the placebo study (at 300 min after the meal 2.7±1.6 ml after placebo and 8.2±3.5 ml after loxiglumide; P<0.008). No difference between placebo and loxiglumide was found in the antral volumes at any time interval (postprandial 63.5±16.5 ml after placebo and 59.4±24 ml after loxiglumide; at 300 min after the meal 20.8±13.3 ml after placebo and 18.9±9.5 ml after loxiglumide). In conclusion, a single oral dose of loxiglumide at the dose of 800 mg can inhibit postprandial gallbladder contraction without affecting gastric emptying. It would therefore appear that in man endogenous CCK, released after a solid-liquid, caloric, nutrient-balanced meal, plays a major role in the contraction of the gallbladder but does not affect gastric emptying.     

Blockade of GRP receptors inhibits gastric emptying and gallbladder contraction but accelerates small intestinal transit

BACKGROUND & AIMS: This study was designed to characterize [D-F(5)Phe(6)D-Ala(11)]Bn(6-13)OMe (BIM26226) as a gastrin-releasing peptide (GRP)-preferring bombesin receptor antagonist and to determine whether GRP physiologically regulates gastrointestinal motility. Intravenous BIM26226 (5-500 microg. kg(-1). h(-1)) inhibits GRP-induced gallbladder contraction and plasma cholecystokinin (CCK) release in a dose-dependent fashion. METHODS: Gastric emptying and small bowel transit of a solid meal were quantified using scintigraphy. Meal-stimulated gallbladder contraction was measured by sonography in a 2-period crossover design. RESULTS: Intravenous BIM26226 potently inhibited gastric lag time (114 +/- 7 vs. 41 +/- 6 minutes [control]) and gastric emptying rate (0.11 +/- 0.02%/min vs. 0.26 +/- 0.04%/min [control]), whereas concomitant infusion of BIM26226 accelerated small bowel transit time (153 +/- 41 vs. 262 +/- 20 minutes [control]). A continuous liquid meal perfusion into the duodenum induced complete gallbladder contraction (t(50%), 35 +/- 4 minutes), which BIM26226 inhibited significantly (t(50%), 64 +/- 8 minutes). BIM26226 did not alter plasma CCK response, indicating that circulating CCK did not mediate these effects. CONCLUSIONS: These data show that BIM26226 is a potent antagonist of exogenous and endogenous GRP and suggest that GRP is a major physiologic regulator of gastric emptying, small bowel transit, and gallbladder contraction.     

Delayed postprandial gastric emptying and impaired gallbladder contraction together with elevated cholecystokinin and peptide YY serum levels sustain satiety and inhibit hunger in healthy elderly persons

BACKGROUND: Altered gastric and cholecystic motility are risk factors for malnutrition in elderly persons, mainly through impaired satiety-appetite rhythm. Contrasting data have been published about this topic. The aim of this study was to evaluate, in healthy elderly participant, postprandial gastric and cholecystic emptying in relation to serum CCK (cholecystokinin) and PYY (peptide YY), as well as satiety and hunger sensations. METHODS: We studied 10 community-dwelling elderly persons, (77 +/- 3 years old) and 9 younger adult persons (32 +/- 8 years old). Using ultrasonography, we measured gastric antrum area and cholecystic volume in fasting condition and after an 800-kcal mixed meal. Time for gastric and cholecystic emptying, and percentage of cholecystic emptying were calculated. Satiety and hunger were evaluated every 30 minutes using visual analogue scales. CCK and PYY serum levels were assayed 30 minutes before and at times 0, 30, 60, 120, and 240 minutes after the meal. RESULTS: Elderly participants showed a longer gastric emptying time compared to younger participants (448 +/- 104 vs 306 +/- 57 minutes, p <.002). Postprandial cholecystic emptying was significantly reduced in the older group (maximum contraction, 69% vs 84%; p <.05). After the meal, CCK and PYY levels showed higher, persistent elevation in elderly participants. In this group, postprandial satiety lasted significantly longer than in younger participants, and hunger was suppressed throughout the postprandial period. Antral area directly correlated with satiety and inversely with hunger. Gallbladder volume inversely correlated to satiety. CONCLUSIONS: This study showed, in a group of healthy elderly people, delayed gastric emptying associated to reduced cholecystic contractility together with higher CCK and PYY serum levels. These modifications facilitated long-lasting satiety and hunger suppression after a meal. This condition may lead to caloric restriction and finally to malnutrition at older ages.     

The effect of acute oral erythromycin on gallbladder motility and on upper gastrointestinal symptoms in gastrectomized patients with and without gallstones: a randomized, placebo-controlled ultrasonographic study

OBJECTIVE: Gastrectomy might be a risk factor for cholelithiasis and gallbladder stasis might play a major role. We studied fasting and postprandial gallbladder motility with 600 mg oral erythromycin or placebo in gastrectomized patients (with and without gallstones) and controls. METHODS: Seventeen patients operated on for gastric cancer (subtotal gastrectomy: n = 10, total gastrectomy: n = 7) were compared with 20 sex- and body-size matched healthy controls. Subjects randomly received erythromycin or placebo 30 min before the ingestion of a standard 200 ml liquid test meal. Gallbladder volume was estimated by ultrasonography until 120 min after test meal. A visual analog scale monitored GI perception of appetite, satiety, nausea, abdominal fullness and epigastric pain. RESULTS: Gastrectomized patients had increased fasting gallbladder volume (35.9 +/- 3.4 ml versus 21.0 +/- 1.4 ml, p = 0.0005) with faster postmeal emptying (T/2 14.8 +/- 1.1 min versus 23.5 +/- 1.5 min, p = 0.00019) than controls. Six patients developed small and asymptomatic gallstones, which did not influence gallbladder motility. In these patients, fasting gallbladder volume increased with time after surgery (r = +0.82, p = 0.047). Perception of satiety, abdominal fullness, and epigastric pain after ingestion of the test meal were all significantly greater in patients than in controls. Erythromycin significantly enhanced gallbladder emptying during fasting (p = 0.001) and postprandially in both patients and controls (0.002 < p < 0.017) and significantly reduced postmeal satiety and epigastric discomfort in gastrectomized patients. CONCLUSIONS: Increased fasting volume might be a form of stasis, predisposing patients to gallstone formation. Erythromycin improves fasting and postprandial gallbladder emptying and decreases upper GI symptoms in gastrectomized patients.     

Effects of cisapride on gallbladder emptying and pancreatic polypeptide and cholecystokinin release in humans

We investigated the effects of cisapride on gallbladder motility and on the release of pancreatic polypeptide and cholecystokinin in the fasting and postprandial states. Cisapride (7.5mg) and/or a test meal was administered intraduodenally to seven healthy volunteers with or without atropine pretreatment (0.5mg, i.m.). In the fasting state, cisapride increased gallbladder volume to 154% of the basal level, and significantly elevated plasma pancreatic polypeptide levels. The effects of cisapride were inhibited by atropine. In the postprandial state, integrated pancreatic polypeptide and cholecystokinin responses were increased by cisapride to 180% and 192%, respectively, of control values. Atropine inhibited the integrated gallbladder and pancreatic polypeptide response to about 60% of the control value but did not affect the cholecystokinin response. These observations suggest that: (1) fasting gallbladder tone is influenced by cholinergic inhibitory mechanisms, (2) acetylcholine (ACh) is the final mediator for about 40% of the postprandial gallbladder emptying and pancreatic polypeptide response, and (3) coordination between the ACh-independent cholecystokinin response and ACh-dependent pancreatic polypeptide response may be important in the regulation of postprandial gallbladder emptying.     

Role of nutrient fat and cholecystokinin in regulation of gallbladder emptying in man

Postprandial gallbladder contraction is mainly regulated by cholecystokinin (CCK), but little is known about the dose-response relationship between CCK release and gallbladder contraction, in particular after meals with differing fat content. Decreased postprandial gallbladder emptying has been suggested to play a major role in the development of gallstones in man, and dietary factors may therefore be important in the pathogenesis of gallbladder stasis. We studied, in a randomized order, the effect of three isocaloric meals (250 ml) with identical osmolality on CCK release and gallbladder contraction in six healthy volunteers: (1) a pure fat meal (25 g triglycerides); (2) a mixed meal containing fat (8 g, 29% of caloric content), protein (10 g, 17%), and dextrose (32 g, 54%); and (3) a fat-free meal containing albumin (25 g, 46%) and dextrose (32 g, 54%). Gallbladder volumes and antral cross-sectional areas were determined by ultrasonography and plasma CCK and PP levels by RIA. The pure fat meal caused the highest CCK release (187±27; mean ±sem) and maximal (>85% of fasting volume) gallbladder contraction (3172±361; AUC) as compared to the other two meals (P<0.05). The mixed and the fat-free meal caused similarly low (<50% of fasting volume) gallbladder contraction (6052±342 and 6134±500, respectively), although they induced markedly different CCK levels (157±12 and 87±13, respectively;P<0.05). Gastric emptying rates were similar for all meals (18,500±3300, 18,600±2700 and 19,800±3100, respectively). The results of this study suggest that CCK plays a major role in the stimulation of gallbladder contraction but that other factors besides CCK are implied when fat-free or low-fat meals are ingested. Furthermore, our findings suggest that a fat intake of 25 g induces maximal gallbladder contraction and may thus prevent an understimulation of gallbladder contraction and the formation of gallbladder stones.     

Severely impaired postprandial gallbladder emptying despite unchanged cholecystokinin release in the early phase of biliary colic

In the present article we report transitory severely impaired postprandial gallbladder emptying preceding biliary colic in a cholesterol gallstone patient. Gallbladder emptying 1 wk before and 3 wk after the biliary colic was normal. Treatment with ursodeoxycholic acid led to increased fasting gallbladder volumes, but the postprandial residual volume did not change. Postprandial cholecystokinin release appeared not to change during ursodeoxycholic acid treatment or during biliary colic.     

Role of free fatty acids in regulating gastric emptying and gallbladder contraction

The limited effectiveness of orlistat, an inhibitor of gastrointestinal lipases, in inhibiting fat digestion is not completely understood. Therefore we studied the effect of orally and duodenally administered orlistat on gastric emptying, cholecystokinin (CCK) secretion, and gallbladder contraction. In healthy males, gastric emptying of solids and fat were quantified scintigraphically, gallbladder contraction by ultrasound and CCK release by radioimmunoassay. Three studies were performed: (1) oral and (2) duodenal orlistat with a fat-containing meal, and (3) duodenal orlistat with a fat-free meal. Gastric emptying rates of solids and fat (T50% accelerated by 16 and by 22%, p < 0.05, respectively) were significantly faster after duodenal perfusion of orlistat; gallbladder contraction and CCK release were reduced under these conditions (p < 0.005, respectively). With oral orlistat no significant effect was documented on these parameters. We conclude that fat hydrolysis is essential in the regulation of fat-induced gastric emptying and gallbladder contraction.     

Gallbladder emptying and somatostatin and cholecystokinin plasma levels in celiac disease

OBJECTIVE: Gallbladder hypomotility in celiac disease has been attributed to decreased cholecystokinin secretion. The possible influence of somatostatin, which inhibits gallbladder motility, however, has never been evaluated. In this study gallbladder emptying and cholecystokinin and somatostatin plasma levels were evaluated in response to a fatty meal in patients with celiac disease at diagnosis and after long-term gluten-free diet and in controls. METHODS: Gallbladder volume and plasma levels of cholecystokinin and somatostatin were measured by ultrasonography and radioimmunoassay, respectively, at 0 time and 30, 60, 75, and 90 min after an oral fatty meal (227 kcal, 45% fat) in 10 celiac patients at diagnosis and after 18 months of successful gluten-free diet and in 10 healthy subjects. The pattern of gallbladder emptying was evaluated by mixed factorial analysis of variance and the curve fitting by multiple regression analysis. RESULTS: Patients at diagnosis had significantly greater fasting gallbladder volume and higher somatostatin plasma levels than controls (25.7 +/- SD 9.7 ml vs 16.8 +/- 7.0 ml, p = 0.021 and 9.3 +/- 4.6 vs 4.8 +/- 3.4 pmol/L, p = 0.023, respectively), significantly lower fatty meal-induced gallbladder ejection fraction (55 +/- 11.2% vs 76 +/- 7.2%, p = 0.005), and cholecystokinin peak and smaller area under the cholecystokinin secretion curve (3.1 +/- 2.3 pmol/L vs 10.5 +/- 6.9 pmol/L, p = 0.028 and 157 +/- 142 pmol/L/90 min vs 453 +/- 229 pmol/L/90 min, p = 0.028, respectively). The two groups had a similar emptying pattern (p = 0.8913) expressed by a significant quadratic term of the emptying function (p = 0.0001). The mean overall emptying volume was significantly greater in patients than in controls (p = 0.0007). Gluten-free diet normalized these findings. CONCLUSIONS: In patients at diagnosis, elevated somatostatin levels were associated with increased gallbladder fasting volume, whereas decreased cholecystokinin secretion was responsible for the reduced gallbladder emptying. Gluten-free diet reversed these abnormalities.     

Obesity does not increase effects of synthetic ghrelin on human gastric motor functions

BACKGROUND & AIMS: Ghrelin is secreted by the stomach and stimulates food intake. Obese individuals have lower fasting plasma ghrelin levels but increased appetite, suggesting greater responses to endogenous ghrelin in obesity. The aim of this study was to compare effects of exogenous ghrelin (at a dose that stimulates growth hormone [GH] release in the physiologic range) versus placebo on gastric emptying, gastric volume, and postprandial symptoms and determine whether body mass (ranging from normal weight to obesity) influences responses to ghrelin. METHODS: After intravenous bolus synthetic human ghrelin (0.33 mug/kg) or saline, we measured plasma GH, gastric volume, and gastric emptying by combined (99m)Tc-single-photon emission computed tomography and scintigraphy ((111)In egg meal, 300 kcal) and postprandial symptoms using visual analogue scales. RESULTS: In 25 obese subjects (5 men and 20 women; body mass index [BMI], 36 +/- 4 kg/m(2)) and 13 female normal-weight (BMI, 22 +/- 2 kg/m(2)) subjects of similar ages, ghrelin increased GH levels (15.0 +/- 2.4 ng/mL) at 40 minutes postinjection and tended to decrease fasting gastric volumes compared with placebo (P = .059). There were no effects of BMI on treatment response and no differences between ghrelin and saline on postprandial (P = .09) or change in (postprandial minus fasting) gastric volumes, gastric emptying, or aggregate postprandial symptoms. Effects of ghrelin did not differ between obese and normal-weight participants. CONCLUSIONS: At doses that stimulate physiologic GH plasma levels, synthetic ghrelin tended to decrease fasting gastric volumes without altering postprandial volumes or gastric emptying in a predominantly female cohort. The data are not consistent with the hypothesis that higher body mass is associated with increased gastric responsiveness to ghrelin.     

Gallbladder Fasting Volume Is Reduced and Gallbladder Postprandial Emptying Is Enhanced by Intravenous Erythromycin

It has been recently shown that erythromycin, amacrolide antibiotic, exhibits prokinetic properties, byenhancing gastric emptying in health and disease and byinducing gallbladder contraction. The aim of the study was to further investigate theeffect of intravenous erythromycin on gallbladdermotility during fasting and postprandial states. In 10healthy male subjects gallbladder emptying was assessed by ultrasonography on three differentoccasions, each in a random sequence, as follows: (1)after giving 300 ml of fresh milk and infusing normalsaline as placebo (postprandial emptying), (2) afterinfusing 200 mg of erythromycin during the fastingstate, and (3) after infusing 200 mg of erythromycinalong with ingestion of 300 ml of fresh milk. Infusionof erythromycin and placebo lasted 10 min. From the emptying curves, the duration of the lag phaseof emptying, the ejection fraction of emptying, and thetime by which maximal emptying was achieved werecalculated. Infusion of erythromycin induced animmediate contraction [lag phase (±SD): 1.3± 2.6 SD min] of the gallbladder by 42.1 ±22% of its initial volume. Infusion of erythromycinduring the postprandial state significantly decreasedthe duration of the lag phase (1.3 ± 3.5 min after erythromycinplus test meal versus 3.6 ± 4.2 min after testmeal only, P < 0.04) and significantly increased theejection fraction (78 ± 8.5% after erythromycinplus test meal versus 60.6 ± 8.5% after test meal only, P <0.0008). It is concluded that intravenously givenerythromycin induces contraction of the gallbladderduring the fasting state and enhances postprandialgallbladder emptying by accelerating the initiation and increasingthe extent of emptying.     

Plasma cholecystokinin, plasma peptide YY and gallbladder motility in patients with slow transit constipation: effect of intestinal stimulation

BACKGROUND/AIM: Because cholecystokinin and peptide YY are gut hormones with potent effects on gastrointestinal motility, we determined whether abnormalities of cholecystokinin and peptide YY exist in slow transit constipation. METHODS: Plasma concentrations of these hormones before, during and after intraduodenal infusion of a liquid meal in 21 patients with slow transit constipation were compared with the results in 8 healthy controls. RESULTS: Fasting levels of plasma cholecystokinin (3.1+/-0.2 vs. 2.4+/-0.2 pM; p = 0.02) were higher in patients. Basal plasma peptide YY (11.4+/-1.4 vs. 8.9+/-0.7 pM; p = 0.1) tended to be higher in patients. After the meal (60-90 min), incremental cholecystokinin (p<0.05), but not peptide YY, was significantly higher in patients. During intraduodenal infusion of the meal (0-60 min), incremental plasma cholecystokinin (251+/-20 pM.min) and peptide YY (1,146+/-186 pM. min) in patients were almost similar to control values (262+/-22 and 901+/-166 pM. min). Gallbladder volumes before, during and after the meal were not different between the 2 groups. Gastric emptying of a solid meal was delayed in the majority of patients (12 of 18). Abnormalities of plasma cholecystokinin were observed only in patients with delayed gastric emptying. CONCLUSION: Plasma levels of cholecystokinin are elevated in the fasting state and decrease more slowly after stimulation, but maximum release in response to intestinal nutrients is not altered in patients with slow transit constipation. The abnormality seems to be confined to a subgroup of patients with delayed gastric emptying.     

Increased Gallbladder Residual Volume in Nonresponders to Extracorporeal Shock Wave Lithotripsy of Gallbladder Stones

In a prospective study of 63 patients, we purposed to determine whether gallbladder contractility or gallbladder volume before biliary lithotripsy are predictors of fragment disappearance. Percentage gallbladder contraction was calculated from the fractional difference in the sonographically measured gallbladder volume after a standard fatty meal. Statistical analysis showed no significant differences in gallbladder contractility between the fragment-free group and the residual-fragment group before (77.2 +/- 12.7% vs. 71.9 +/- 19.3%; p = 0.1044) biliary lithotripsy and after the termination of adjuvant cholelitholysis therapy (76.4 +/- 12.9% vs. 72.2 +/- 17.1%; p = 0.1341). Before treatment, there was no significant difference in fasting gallbladder volume in either group (29.9 +/- 15.4 ml vs. 36.6 +/- 18.8; p = 0.0682), but postprandial gallbladder volume was greater in nonresponders (10.4 +/- 9.4 ml vs. 6.5 +/- 3.8; p = 0.0164). After termination of the therapy, both the fasting gallbladder volume (41.2 +/- 24.2 ml vs. 29.8 +/- 10.3 ml; p = 0.0093) and the postprandial gallbladder volume (11.9 +/- 11.7 ml vs. 7.3 +/- 5.3 ml; p = 0.0267) were greater in the residual-fragment group. The increase of the fasting gallbladder volume in the residual-fragment group was statistically not significant. Our results indicate that the increased residual volume is a significant cause of therapeutic failure in nonresponders.     

Ghrelin stimulates gastric emptying and hunger in normal-weight humans

CONTEXT: Ghrelin is produced primarily by enteroendocrine cells in the gastric mucosa and increases gastric emptying in patients with gastroparesis. MAIN OBJECTIVE: The objective of the study was to evaluate the effect of ghrelin on gastric emptying, appetite, and postprandial hormone secretion in normal volunteers. DESIGN: This was a randomized, double-blind, crossover study. SUBJECTS: Subjects included normal human volunteers and patients with GH deficiency. INTERVENTION: Intervention included saline or ghrelin (10 pmol/kg.min) infusion for 180 min after intake of a radioactively labeled omelette (310 kcal) or GH substitution in GH-deficient patients. MAIN OUTCOME MEASURES: Measures consisted of gastric empty-ing parameters and postprandial plasma levels of ghrelin, cholecystokinin, glucagon-like peptide-1, peptide YY, and motilin. RESULTS: The emptying rate was significantly faster for ghrelin (1.26 +/- 0.1% per minute), compared with saline (0.83% per minute) (P < 0.001). The lag phase (16.2 +/- 2.2 and 26.5 +/- 3.8 min) and half-emptying time (49.4 +/- 3.9 and 75.6 +/- 4.9 min) of solid gastric emptying were shorter during ghrelin infusion, compared with infusion of saline (P < 0.001). The postprandial peak in plasma concentration for cholecystokinin and glucagon-like peptide-1 occurred earlier and was higher during ghrelin infusion. There was no significant effect of ghrelin on plasma motilin or peptide YY. There was no difference in gastric emptying before and after GH substitution. CONCLUSION: Our results demonstrate that ghrelin increases the gastric emptying rate in normal humans. The effect does not seem to be mediated via GH or motilin but may be mediated by the vagal nerve or directly on ghrelin receptors in the stomach. Ghrelin receptor agonists may have a role as prokinetic agents.     

Cephalic stimulation of gallbladder contraction in humans: role of cholecystokinin and the cholinergic system

To determine the role of cholecystokinin and the cholinergic system in cephalic stimulation of gallbladder contraction and to compare the degree of gallbladder contraction by cephalic stimulation with postprandial gallbladder contraction, 8 healthy volunteers (4 males, 4 females, 20-65 years) underwent the following studies: sham feeding of an appetizing meal, sham feeding with intravenous atropine, and ingestion of the same meal. Gallbladder volume was measured by real-time ultrasonography and plasma cholecystokinin by a sensitive and specific radioimmunoassay using antibody T204. Gallbladder contraction in response to sham feeding, 30 +/- 4% (p = 0.0001 vs. basal), amounted to half of that seen after real feeding, 69 +/- 5% (p less than 0.0001 vs. basal). Significant dissociation between gallbladder response to sham feeding and real feeding was seen from 40 min (p less than 0.005-p = 0.0001). Atropine did not affect basal gallbladder volume but completely abolished gallbladder contraction in response to sham feeding. Neither sham feeding without nor sham feeding with atropine significantly affected plasma cholecystokinin levels. On the other hand, real feeding induced significant increases in plasma cholecystokinin from a basal level of 2.3 +/- 0.1 pM to a peak value of 5.9 +/- 0.4 pM at 40 min. It is concluded that an important cephalic phase of postprandial gallbladder contraction exists which is cholecystokinin-independent but dependent on a cholinergic mechanism.     

Gallbladder and gastric motility in obese newborns, pre-adolescents and adults

Background and Aim: Impaired gallbladder and gastric motility have been associated with obesity in adults. The timing of appearance of this dysfunction, however, is unclear. Methods: Lean and obese subjects from three different age groups were studied noninvasively: 50 newborns (1–12 months old, six obese), 18 pre‐adolescents (7–8 years old, seven obese), and 99 adults (22–80 years old, 32 obese) classified according to standard normal tables and body mass index. Changes of fasting/postprandial gallbladder and gastric motility were assessed simultaneously by functional ultrasonography in response to milk (newborns and pre‐adolescents) and to a liquid test meal (adults). Results: In newborns, fasting and postprandial gallbladder volumes and gastric emptying were similar between obese and lean subjects. In pre‐adolescents, obese subjects had a larger fasting gallbladder volume, with slower postprandial gastric emptying than lean subjects. In obese adults, the most evident dysfunction emerged, with larger fasting and postprandial residual gallbladder volume, and slower postprandial gastric emptying than lean subjects. Conclusions: Obese subjects display abnormal gallbladder and gastric motility patterns, which first appear in pre‐adolescents and deteriorate in adults. Such abnormalities are absent in obese newborns. Functional ultrasonography can detect altered cholecysto‐gastric motility at the earliest stage. Our findings suggest an age‐related decline of motility, probably secondary to excessive fat and insulin‐resistance.     

Physiological role of cholecystokinin on postprandial insulin secretion and gastric meal emptying in man. Studies with the cholecystokinin receptor antagonist loxiglumide

Summary Cholecystokinin was previously proposed to play an important role in the regulation of postprandial insulin secretion either indirectly, by inhibiting gastric meal emptying, or directly, by acting as an incretin promoting the release of insulin. The aim of this investigation was therefore to clarify the role of endogenous cholecystokinin in the regulation of insulin release and gastric emptying applying the highly potent and specific cholecystokinin receptor antagonist loxiglumide. Five healthy volunteers were examined after an overnight fast. Gastric meal emptying was measured by the double indicator technique using a multiple lumen tube in the duodenum and ^99mTc-diethylenetriamine pentaacetate as a meal marker and polyethylene glycol 4000 as a duodenal perfusion marker. Postprandial insulin, C-peptide, cholecystokinin and glucose levels were measured after ingestion of two isocaloric meals of a) Ensure (containing fat, protein and glucose), and b) a pure glucose meal (1.11 mol/l). The meals were given either with an intravenous infusion of loxiglumide (22 mol·kg^–1·h^–1) or placebo. The infusion of loxiglumide markedly accelerated the gastric emptying of the mixed meal (area under curve, 5576±352 min vs 3498±109 min; p<0.001) and the pure glucose meal (area under curve 5662±537 min vs 3551±534 min; p<0.05). Simultaneously, loxiglumide induced a more rapid rise in postprandial insulin levels after both meals resulting in significantly higher (p<0.05) insulin levels during the first postprandial hour, but similar insulin levels in the second postprandial hour. Accordingly, we found a close correlation between meal emptying and insulin release (r=0.748, p<0.01). Integrated insulin and C-peptide levels for the whole 2-h experimental period tended to be higher during loxiglumide infusion, but the difference did not reach statistical significance. Similar plasma glucose levels at all time periods were observed with and without loxiglumide infusion. Higher cholecystokinin levels were measured during loxiglumide infusion after the mixed (p<0.01) and the pure dextrose (p<0.05) meals. We conclude that postprandially released cholecystokinin exerts an important role in the regulation of gastric meal emptying and consecutively the postprandial pattern of insulin release. In contrast, no evidence was found for an insulinotropic role for cholecystokinin in man.