Gallbladder sensitivity to cholecystokinin in coeliac disease. Correlation of gallbladder contraction with plasma cholecystokinin-like immunoreactivity during infusion of cerulein.

The present study was undertaken to determine whether alterations in the gallbladder sensitivity to cholecystokinin (CCK), apart from a reduced endogenous CCK secretion, contribute to the abnormally decreased postprandial gallbladder contraction in patients with coeliac disease. Gallbladder emptying, measured by cholescintigraphy, and plasma CCK levels, measured by radioimmunoassay, were studied during infusion of graded doses of the CCK analog cerulein in six coeliac patients with subtotal villous atrophy, six coeliac patients on a gluten-free diet with normal villous architecture, and nine control subjects. Both in the patients and in the controls infusion of stepwise increasing doses of cerulein, in the range of 1-16 ng.kg-1.h-1, induced dose-related changes in plasma CCK-like immunoreactivity (CCK-LI) (r = 0.99; p less than 0.001) and gallbladder emptying (r greater than 0.97; p less than 0.01-p less than 0.001). Plasma CCK-LI and gallbladder responses were not significantly different among untreated coeliac patients, treated coeliac patients, and controls. Gallbladder sensitivity to cerulein in untreated and treated coeliac patients was not significantly different from that in controls. It is concluded that the abnormally decreased gallbladder contraction in coeliac patients is the result of a reduced endogenous CCK secretion and not of a lack of end-organ responsiveness to CCK.     

Neurohumoral control of gallbladder motility in healthy subjects and diabetic patients with or without autonomic neuropathy

Patients affected by diabetes mellitus are reported to have an increased incidence of gallbladder abnormalities. The pathophysiologic mechanisms for this phenomenon are unclear. In the present study ultrasonography was used to determine gallbladder emptying in response to a meal or separate cephalic or hormonal stimulation in 21 diabetic patients and 10 healthy subjects. Gallbladder emptying and refilling after a meal were similar in diabetic patients and healthy subjects. When diabetics were divided according to the presence or absence of cardiac autonomic neuropathy (AN), a significant reduction of gallbladder emptying in response to cephalic stimulation was found in diabetics with AN (P<0.01 in comparison with diabetics without AN or healthy subjects). A dose-response curve of gallbladder emptying in response cerulein, a cholecystokinin analog, at concentrations of 0.25, 1, and 4 g/kg/min was evaluated. No differences of gallbladder emptying were found in the three groups of subjects, indicating that gallbladder sensitivity to hormonal stimulation is not changed in diabetic patients with or without AN. Diabetic patients with AN have a significant reduction of gastric acid output and pancreatic polypeptide (PP) secretion in response to cephalic stimulation (P<0.05 in comparison with diabetic patients without AN or healthy subjects). Cerulein-induced PP secretion was similar in all three groups of subjects (P>0.05). This study indicates that in diabetic patients with AN, gallbladder emptying as well as gastric acid and PP secretions induced by neural stimulation are markedly reduced in comparison to diabetics without AN.     

Pancreatic polypeptide response to food and cerulein in patients with total gastrectomy

In order to investigate the intestinal phase of pancreatic polypeptide (PP) release, the hormonal response to food and cerulein was measured in 19 patients with truncal vagotomy and total gastrectomy (10 with simple esophagojejunal anastomosis and 9 with an additional duodenojejunal anastomosis) and in 7 healthy subjects. After gastrectomy, the early peak of the physiologic biphasic PP response to food was lost but the late predominant phase was unchanged so that the overall postprandial release of the hormone was not significantly lowered. Gastrectomized patients with duodenal bypass had postprandial serum levels only slightly lower than those of patients with preserved duodenal transit of food. Serum PP response to cerulein stimulation was significantly lower in vagotomized patients than in healthy subjects. However, in operated patients as well as in controls, cerulein infusion did induce a rapid increase of plasma PP, followed by persistently elevated levels. The PP response to cerulein was abolished by atropine pretreatment. Our findings indicate that the intestinal phase of meal-stimulated PP response is not dependent on the integrity of vagal pancreatic innervation and that the preservation of the duodenal transit of food after total gastrectomy is not crucial for the maintenance of the enteroinsular axis.     

Gallbladder Emptying to Endogenous and Exogenous Stimulation in Chronic Pancreatitis Patients

Objectives : The present study was designed to analyze the underlying mechanism of gallbladder motor disturbance in chronic pancreatitis patients. Methods : Gallbladder emptying to endogenous (oral test meal, Daiyan 13 g) and exogenous stimulation (iv cerulein, 30 ng/kg for 5 min) was examined by real-time ultrasonography in 12 patients with chronic pancreatitis and 10 normal subjects (controls). Plasma cholecystokinin levels during the endogenous stimulation were measured by bioassay. Results : In chronic pancreatitis patients compared with controls, the fasting allbladder volume was significantly increased (29.5 ± 2.2 vs. 21.5 ± 2.8 ml), whereas the gallbladder emptying (percent change of the basal volume) to oral test meal was significantly decreased. Neither cholecystokinin secretion induced by the test meal, nor the gallbladder emptying response to intravenous cerulein, differed signiHcantly between the two groups. However, when chronic pancreatitis patients were divided according to pathogenesis, it became clear that gallbladder emptying to intravenous cerulein was significantly greater in patients with alcoholic chronic pancreatitis than in patients with idiopathic pancreatitis. Conclusions: Gallbladder emptying during the intestinal phase Is generally reduced in patients with chronic pancreatitis, but gallbladder responsiveness to exogenous stimulation might be heterogeneous according to the pathogenesis.     

ABNORMAL PANCREATIC POLYPEPTIDE RESPONSE TO ORAL GLUCOSE LOADING IN DIABETES MELLITUS

In order to elucidate the abnormality of pancreatic polypeptide (PP) secretion in diabetes mellitus, basal plasma PP levels and their response to oral glucose loading were measured in normal subjects and diabetic patients. Fasting plasma PP levels were significantly elevated in patients with diabetes mellitus. Oral administration of 50g of glucose elicited an exaggerated rise in plasma PP in diabetic patients as compared with the response in normal subjects. This exaggerated PP response to oral glucose loading was partially but significantly improved after the treatment, with an augmented response of plasma insulin. These results indicate the existence of abnormal PP secretion in diabetes mellitus which is possibly caused by metabolic or endocrine derangements.     

Gallbladder emptying in duodenal ulcer patients having undergone Billroth II gastrectomy

There is an increased incidence of gallstones in patients who have undergone Billroth II (BII) gastrectomy for duodenal ulcer. To explore the mechanisms underlying this, we examined changes in gallbladder volume induced by a meal and by intravenous administration of cerulein, in 13 BII patients and in 13 normal subjects. Gallbladder volume was measured by real-time ultrasonography. In the fasting state, gallbladder volumes were significantly larger in BII patients than in controls. The percent decrease in gallbladder volume after the meal was significantly less and maximum volume reduction observed throughout the study occurred sooner in BII patients than in controls. In contrast, the kinetics and magnitude of the reduction in gallbladder volume induced by cerulein were similar in the two groups. These findings suggest that the altered gallbladder response to a meal is due to impaired postprandial stimulation of gallbladder following BII gastrojejunostomy.     

Role of cholecystokinin in bombesin- and meal-stimulated pancreatic polypeptide secretion in dogs

This study was undertaken to delineate the role of cholecystokinin (CCK) in bombesin- and meal-stimulated pancreatic polypeptide (PP) secretion in seven conscious dogs by studying: (1) the stimulatory effect of similar plasma levels of CCK induced by a meal and infusions of bombesin and the synthetic CCK analog cerulein on plasma PP, and (2) the inhibition of PP secretion by the CCK-receptor antagonist CR-1409 during these three stimuli. The stimulation of PP secretion during bombesin (11.0±1.6 nM/hr) and after the meal (8.9±2.0 nM/hr) were significantly (P<0.05) greater than during infusion of the CCK analog cerulein (2.7±0.4 nM/hr). CR-1409 significantly inhibited the bombesin- and meal-stimulated PP secretion to 2.0±0.4 nM/hr (81%; P<0.05) and 3.1±1.2 nM/hr (47%; P<0.05), respectively, while the cerulein-stimulated PP release was almost abolished to 0.2±0.1 nM/hr (93%; P<0.05) by the drug. These findings point to an important role for CCK in the regulation of bombesin- and meal-stimulated PP secretion.Supported by grant 13-37-43 from the Netherlands Foundation for Medical Research MEDIGON and grant Si 228/7-1 from the Deutsche Forschungsgemeinschaft.     

Cholecystokinin (CCK) in the amino acid uptake and enzyme protein secretion by the pancreas in humans

Summary Activation of type A receptors by CCK or cerulein is known to stimulate pancreatic enzyme secretion, but its role in the amino acid (AA) consumption and enzyme synthesis remains unclear. In our study, we used loxiglumide, a potent CCK-A-receptor antagonist, to investigate the role of CCK-A receptors in pancreatic consumption of circulating AAs and enzyme secretion. Five healthy male volunteers were intubated with double-lumen duodenal tube, and duodenal aspirates were collected during 60-min basal periods and then during pancreatic stimulation with iv infusion of secretin (80 pmol/kg/h) plus cerulein (50 pmol/kg/h) during three consecutive 30-min periods. The same procedure was repeated, but secretin-cerulein infusion was combined with a constant dose of loxiglumide (20 μmol/kg/h). The volume and outputs of HCO₃ ⁻, protein and enzymes (amylase and trypsin) in duodenal aspirates and gallbladder volume (by sonography) were determined at 30-min intervals. Plasma samples were drawn for total plasma AA assay by ninhydrin method to assess the pancreatic uptake of free AAs. Infusion of secretin plus cerulein caused a several-fold increase in the volume of duodenal aspirate and the outputs of HCO₃ ⁻, protein, and enzymes. During those periods, plasma AA level decreased from initially 2.20±0.3 mmol/L to 1.09±0.3 mmol/L (p<0.01) and the gallbladder volume from initially 28±8 mL to 2±0.4 mL. This increase in pancreatic secretory outputs was accompanied by significant increments in plasma insulin, glucagon, PP, and somatostain. After addition of loxiglumide to the secretin-cerulein infusion, the pancreatic volume and HCO₃ ⁻ outputs were unchanged, but the increments in protein and enzyme outputs and in plasma hormone levels decreased to preinfusion values. The total plasma AA level remained, however, unchanged after loxiglumide. Addition of loxiglumide almost completely prevented the contraction of the gallbladder. These results indicate that CCK-A receptors are involved in the secretin-cerulein-stimulated exocrine pancreatic protein enzyme secretion and islet hormone release, but do not appear to be involved in the pancreatic AA consumption.     

Plasma cholecystokinin and gallbladder responses to intraduodenal fat in gallstone patients

Impaired gallbladder emptying is one of the various factors suggested to be involved in the pathogenesis of gallstones. The present study was undertaken to determine whether gallbladder emptying, endogenous cholecystokinin (CCK) secretion, or their interrelation is altered in patients with gallstones. After intraduodenal administration of 60 ml corn oil, plasma CCK concentration was measured by a sensitive and specific radioimmunoassay and gallbladder emptying by cholescintigraphy. Patients with gallstones (N=20) produced significantly less endogenous CCK (105±17 pmol/liter 60 min; P <0.001) than control subjects (191±11 pmol/liter 60 min, N=20); gallbladder emptying in the patients was significantly decreased at 5, 10, 40, 45, and 50 min but the reduction in gallbladder emptying did not reach statistical significance at 60 min (patients 44±8%, control subjects 60±4%). In addition, the gallbladder responsiveness to intravenous infusion of the synthetic CCK analog cerulein was investigated. Based on the results of gallbladder emptying in response to endogenous and exogenous CCK, four subgroups of gallstone patients were identified: (1) a group (N=7) with normal gallbladder sensitivity to CCK, (2) a group (N=6) with significantly increased gallbladder sensitivity to CCK, (3) a group (N=6) with impaired gallbladder emptying after corn oil due to a significantly reduced endogenous CCK secretion but with normal gallbladder sensitivity to CCK, and (4) one patient whose gallbladder was unresponsive to CCK and was found to have chronic cholecystitis at surgery.     

Postprandial gallbladder motility and plasma cholecystokinin at regular time intervals after injection of octreotide in acromegalics on long-term treatment

The increased risk of gallstone formation in acromegalics treated with the somatostatin analog octreotide has been related to an impaired gallbladder emptying. To determine the duration of these inhibitory effects, meal-stimulated gallbladder motility, plasma cholecystokinin (CCK), and pancreatic polypeptide (PP) were measured in five acromegalics treated for 6–32 months with 200–300 g octreotide daily. Meal tests were performed 45 min, 8 hr and two weeks after the last 100-g subcutaneous dose. Results were compared with those in normal subjects. Integrated postprandial gallbladder contraction (–125±194 cm³/120 min) and integrated PP secretion (–0.1±0.2 nmol/liter/120 min) were completely suppressed in the 45-min study, but significantly improved (P<0.05) when measured 8 hr (1376±322 cm³/120 min and 3.0±1.0 nmol/liter/120 min) and two weeks (1437±263 cm³/120 min and 10.6±1.6 nmol/liter/120 min) after the last dose of octreotide. The integrated gallbladder contraction in acromegalics at 8 hr was comparable to that at two weeks and to that in normal subjects, but the integrated PP response at 8 hr was significantly smaller (P<0.05 vs two weeks and vs normals). Integrated plasma CCK secretion at 45 min (0.13±0.06 nmol/liter/120 min) was not statistically significantly different from the response at 8 hr (0.15±0.02 nmol/liter/120 min) and from that in normal subjects, but it was significantly increased at two weeks after cessation of octreotide (P<0.05 vs 45 min and 8 hr). In conclusion, during long-term octreotide treatment in acromegalics, initial abolishment of postprandial gallbladder emptying is completely reverted to normal values 8 hr after the last subcutaneous dose. No major differences in postprandial plasma CCK at 45 min and at 8 hr were observed when compared with normal subjects, whereas plasma PP responses were diminished.     

Duodenal acid is without importance for the postprandial PP release

In six healthy subjects duodenal infusion of 30 ml 100 mmol/1 HCl caused a slight, but significant, release of plasma pancreatic polypeptide (PP), whereas infusion of 3 g dried cattle bile dissolved in 30 ml distilled water did not affect basal plasma PP levels. In another group of six healthy subjects the postprandial plasma PP release was not affected by inhibition of the gastric H+ secretion by the H2-receptor antagonist ranitidine. Finally, the meal-induced plasma PP release in a group of 19 achlorhydric patients did not differ significantly from that seen in 11 normal controls. We therefore conclude that, although duodenal acidification may elicit release of plasma PP, gastric H+ secretion seems to be without importance for the postprandial plasma PP release.     

Modulation of Gallbladder Contraction by Pirenzepine in Humans

Objectives : The mechanism (s) by which cholinergic innorvatiun modulates gallbladder contraction are not fully understood. To elucidate the role of muscarinic M, receptors in the mediation of gallbladder contraction, we investigated gallbladder volume reduction, plasma cholecystokinin (CCK). and pancreatic polypeptide (I'P) responses in humans during cephalic and intestinal phases of a meal under M, muscarinic receptor blockade with pirenzepine. Methods : In eight healthy subjects, intruduodenal meal- and in seven subjects, sham feeding-induced gallbladder volume reduction was measured by real-time ultrasonography during saline or piren/-epine administration. Plasma CCK and PP were measured by radioimmunoassay. Results : Pirenzepine partially inhibited gallbladder volume reduction in response to an intraduodenal fatty meal. The integrated gallbladder volume reduction over 120 min was 4462 ± 445%.min compared with 6879 ± 279%.min in the saline control group ( p < 0.01). Integrated plasma CCK and PP responses were unchanged in the presence of pirenzepine. Pirenzepine abolished sham feeding-induced gallbladder contraction and plasma PP response. Sham feeding with either isotonic saline or pirenzepine infusion did not modify fasting plasma CCK levels. Conclusion : M, muscarinic receptors play an important role in the intestinal and cephalic phases of gallbladder contraction. Plasma CCK response to intraduodenal meal is not influenced by M, muscarinic receptor blockade with pirenzepine.     

Gallbladder emptying and cholecystokinin and pancreatic polypeptide responses to a liquid meal in patients with diabetes mellitus

To investigate gallbladder motility and its regulation in patients with diabetes mellitus (DM), we examined the gallbladder response to an intraduodenal test meal by measuring the temporal course of plasma cholecystokinin (CCK) and pancreatic polypeptide (PP) levels. Eighteen patients with type 2 DM and 7 healthy subjects (controls) were enrolled. The gallbladder volume was calculated by the sum-of-cylinders method from ultrasonographic images, and plasma CCK and PP were measured by radioimmunoassays. No significant difference was found in either the gallbladder response or in the CCK response between patients with DM and controls. However, the fasting plasma PP level of patients with DM was more than tenfold higher than that of controls. The integrated PP response (IPPR) of patients with DM to the test meal was 8.3-fold higher than that of controls. When patients with DM were grouped according to whether they had been treated with insulin or not, the fasting plasma PP of patients with DM without insulin treatment was significantly higher than the level in those treated with insulin. These results suggest that overproduction of PP-like immunoreactive substance(s) may occur in patients with DM, but the high plasma PP immunoreactivity does not appear to be related to the fasting gallbladder volume or to gallbladder emptying and filling.     

Pancreatic polypeptide response in patients with chronic pancreatitis

We studied the plasma pancreatic polypeptide (PP) response to a meal in patients with pancreatitis and attempted to correlate the PP increment with the degree of pancreatic exocrine insufficiency. Control subjects and patients with recurrent pancreatitis showed significant mean increase (P<0.05) in plasma PP concentration in response to food. By contrast chronic pancreatitis patients had no significant increase in plasma PP. However, some subjects with normal pancreatic secretion had no response and some patients with chronic pancreatitis did show a response. In addition, no correlation was observed between the PP response and pancreatic exocrine secretion. We conclude that the PP response to a meal has only limited value in the detection of pancreatic destruction.     

Cholecystokinin secretion is suppressed by glucagon-like peptide-1: clue to the mechanism of the adverse gallbladder events of GLP-1-derived drugs

Abstract

Objective: Recent randomized and controlled trials of drugs derived from the gut hormone glucagon-like peptide-1 (GLP-1) show that the most frequent adverse symptoms are gastrointestinal, including gallbladder-related side effects such as cholithiasis and cholecystitis. Since the gut hormone cholecystokinin (CCK) stimulates bile secretion and regulates gallbladder motility and emptying, we examined the effect of GLP-1 on the secretion of CCK in normal subjects and patients with type 1 diabetes mellitus.

Materials and methods: Plasma was sampled from 10 healthy subjects and 10 patients with diabetes. With plasma glucose concentrations clamped between 6 and 9?nmol/l, GLP-1 or saline was infused for 240?min during and after a meal. The plasma concentrations of CCK were measured with a highly specific radioimmunoassay.

Results: Basal plasma concentrations of CCK were similar in the normal subjects and in the diabetes patients. During the meal, the CCK concentrations rose significantly during saline infusion, whereas the GLP-1 infusion suppressed the secretion of CCK significantly in both normal subjects and in the diabetes patients.

Conclusions: The results show that GLP-1 suppresses the secretion of CCK after a meal in normal and diabetic subjects. The suppression attenuates the gallbladder contractility. Our data, therefore, offer an explanation for the increased risk of adverse gallbladder events during treatment with GLP-1-derived drugs.     

Atropine Antagonizes Cholecystokinin and Cerulein-Induced Gallbladder Evacuation in Man: A Real-Time Ultrasonographic Study

Dose-response curves for cholecystokinin (CCK), cerulein (CRL), and the effect of atropine on peptide-induced gallbladder evacuation, were evaluated in 13 normal subjects. Gallbladder volume was monitored by means of real-time ultrasonography. After an overnight fast, CCK was infused in six subjects iv, with increasing doses from 0.002 IDU/kg/min for 15 min, and CRL in seven subjects from 0.5 ng/kg/min for 5 min, until maximum gallbladder evacuation (greater than 70% of the fasting volume) was achieved. Forty-eight hours after the first study, CCK and CRL were readministered at the maximum contracting dose in each subject with and without a pretreatment with atropine (1 mg iv as bolus). The results showed maximum gallbladder evacuation at 0.016 IDU for CCK, and at 4 ng for CRL. Atropine significantly blunted the gallbladder response both to CCK and to CRL. It is therefore suggested that the cholinergic system is involved in the gallbladder response to CCK and to CRL.     

Elemental diet stimulates gallbaldder contraction and secretion of cholecystokinin and pancreatic polypeptide in man

This study was undertaken to investigate the effect of ingestion of 80 g Vivonex on gallbladder volume, plasma cholecystokinin (CCK), and pancreatic polypeptide (PP) in eight healthy volunteers and to compare the results with those obtained after ingestion of 60 ml corn oil. Gallbladder volumes were measured by ultrasonography. Plasma CCK was determined by radioimmunoassay using region-specific antibodies; antibody 1703 binds to COOH-terminal CCK-peptides containing at least 14 amino acid residues, while antibody T204 binds to COOH-terminal CCK-peptides containing the sulfated tyrosine region. Plasma PP was also measured by radioimmunoassay. Ingestion of Vivonex induced significant increases in plasma CCK (0.6±0.1 to 4.6±0.6 pM, antibody 1703; 1.8±0.3 to 5.9±0.5 pM, antibody (T204;P<-0.0005) and decreases in gallbladder volume (21.4±2.8 to 11.2±2.3 cm³;P=0.0001). Integrated plasma CCK secretion and gallbladder contraction after Vivonex were not significantly different from the results found after corn oil. Both Vivonex and corn oil-induced small increases in plasma PP. We conclude that Vivonex is a potent stimulus for the secretion of CCK and contraction of the gallbladder.Supported by the Netherlands Foundation for Medical Research FUNCO (grants 13-37-32 and 13-37-43).     

Gallbladder dynamics and plasma cholecystokinin responses after meals, oral water, or sham feeding in healthy subjects

To investigate the mechanisms controlling human gallbladder contraction, especially to determine the role of neural factors, the gallbladder response to various stimuli was evaluated in eight normal subjects using realtime ultrasonography. In addition, plasma cholecystokinin (CCK) levels were measured using a region-specific antibody (OAL 656). Intramuscular injections of CCK-8 and of cerulein induced mean maximal ejection fractions (EF max) of 50% +/- 6% and 58% +/- 4%, respectively. The mean EF max after ingestion of a fatty meal was 44% +/- 3%, while the EF max after a fat-restricted meal was significantly lower (17% +/- 4%). Oral water and sham feeding also significantly induced gallbladder contractions (EF max; 25% +/- 4% and 12% +/- 4% respectively) that were eliminated by premedication with atropine. The plasma CCK rose significantly after exogenous administration of CCK-8 and after ingestion of a fatty meal. The peak CCK concentration released after fatty meals was almost identical to that after exogenous CCK-8 loading. In contrast, plasma CCK levels showed no change after the fat-restricted meal, oral water and sham feeding. These findings suggest that not only CCK but also the cholinergic pathway may play important roles in the control mechanism of human gallbladder contraction.     

Effect of partial gastrectomy with Billroth II or Roux-en-Y anastomosis on postprandial and cholecystokinin-stimulated gallbladder contraction and secretion of cholecystokinin and pancreatic polypeptide

This prospective study was undertaken to determine the effect of partial gastrectomy without vagotomy on postprandial gallbladder contraction and secretion of cholecystokinin (CCK) and pancreatic polypeptide (PP) in 22 peptic ulcer patients randomly assigned to either Billroth II (N = 11) or Roux-en-Y (N = 11) anastomosis. The patients were studied within two weeks before surgery and at six months postoperatively. After surgery basal gallbladder volumes were larger than preoperatively (P less than 0.02). Integrated postprandial gallbladder contraction was not significantly affected by gastrectomy, either in the patients with Billroth II anastomosis (2276 +/- 268 vs 1985 +/- 362%/60 min) or in those with Roux-en-Y anastomosis (2045 +/- 327 vs 2445 +/- 352%/60 min) when studied pre- and postoperatively, respectively. Similarly, integrated postprandial plasma CCK secretion was not significantly changed by either Billroth II gastrectomy (200 +/- 31 vs 166 +/- 21 pM/60 min) or Roux-en-Y gastrectomy (146 +/- 26 vs 147 +/- 12 pM/60 min). However, integrated postprandial PP secretion was significantly (P less than 0.05) lower after Billroth II gastrectomy (6.8 +/- 2.4 vs 2.2 +/- 1.0 nM/60 min), while the reduction in plasma PP after Roux-en-Y gastrectomy just failed to reach statistical significance (6.0 +/- 1.5 vs 3.4 +/- 0.9 nM/60 min). Similarly, the PP response, but not the gallbladder response, to an intravenous bolus injection of 1 IDU CCK/kg body weight was significantly decreased after gastrectomy independent of the type of anastomosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of intravenous glucose on intravenous amino acid-induced gallbladder contraction and CCK secretion

The present study was undertaken to investigate the effect of acute hyperglycemia on the gallbladder contraction induced by intravenous administration of high doses of amino acids (Vamin 18, 250 mg protein/kg/hr). Six healthy volunteers were studied in random order on two occasions during normoglycemia and hyperglycemia with blood glucose levels stabilized at 15 mmol/liter. Gallbladder volumes, measured with ultrasonography, were studied for 60 min before and for 120 min during intravenous infusion of amino acids (IVAA). Administration of IVAA resulted in a significant reduction (P<0.05) in gallbladder volume from 32±5 cm³ to 17±2 cm³ during normolgycemia. During hyperglycemia no significant changes in gallbladder volume were observed in response to IVAA. No significant changes in plasma CCK concentration, the major hormonal stimulus for gallbladder contraction, occurred in response to IVAA. During hyperglycemia, pancreatic polypeptide (PP) secretion, as an indirect measure of vagal cholinergic tone, in response to IVAA was significantly (P<0.05) reduced compared to normoglycemia. It is concluded that: (1) administration of high doses of IVAA results in significant gallbladder contraction, (2) high doses of IVAA do not stimulate CCK secretion, (3) acute hyperglycemia inhibits IVAA-induced gallbladder contraction, and (4) acute hyperglycemia inhibits basal and stimulated plasma PP secretion, suggesting impaired vagal-cholinergic tone during hyperglycemia.