Plasma Cholecystokinin Levels Research Articles

Chronic diversion of bile to the urinary bladder induces pancreatic growth in dogs

The aim of this study was to elucidate the mechanism of chronic biliary diversion and its effect on pancreatic growth. In the first part of the study, nine mongrel dogs underwent diversion of bile from the gastrointestinal tract by ligating the common bile duct and interposing a segment of jejunum between the gallbladder and the urinary bladder (cholecystojejunocystostomy [CJC]). Despite the loss of 7% of their body weight at 12 weeks after bilioenteric diversion, CJC dogs had significantly greater pancreatic wet weight than control dogs (51.2 ± 2.2 g vs. 37.1 ± 2.2 g). In the second part of the study, six other dogs underwent CJC. Twelve weeks later, bilioenteric continuity was restored by creating a cholecystojejunoduodenostomy (CJD). The dogs were given butter (3 g/kg) by mouth (prior to surgery, 12 weeks after CJC, and 4 weeks after CJD). Pancreatic excisional biopsy specimens were obtained at each operation and at autopsy. CJC induced more pancreatic RNA per milligram of weight (743 ± 52, CJC; 579 ± 44, prior to surgery, P <0.05 vs. CJC; 520 ± 26 μg/100 mg · tissue, CJD, P <0.01 vs. CJC), but not more DNA, and significantly higher basal plasma cholecystokinin levels and butter-stimulated cholecystokinin responses when compared with values prior to surgery or following CJD. We conclude that chronic biliary diversion induces pancreatic growth associated with hypersecretion of cholecystokinin in dogs.

Proximal and distal gut hormone secretion in slow transit constipation.

It has been suggested that slow transit constipation might be part of a panenteric disorder. Gastrointestinal peptides are involved in regulation of motility. In the present study we have evaluated whether plasma levels of proximal and distal gut hormones in the fasting state, and for 120 min after a solid meal in 29 patients with slow transit constipation are different from those obtained from 29 healthy controls. Plasma levels of the gut hormones cholecystokinin, gastrin, pancreatic polypeptide, motilin, neurotensin and peptide YY were determined using sensitive radioimmunoassays. In the patient group, oro-caecal transit time was determined by means of the hydrogen breath test on a separate test day. The results of transit were related with postprandial hormone secretion. Fasting plasma levels of cholecystokinin and pancreatic polypeptide were significantly (P < 0.05) increased in constipated patients. Postprandially, secretion of pancreatic polypeptide and cholecystokinin was significantly (P < 0.05) increased in the patients, while secretion of peptide YY was significantly (P < 0.05) reduced. Plasma motilin levels were not different between patients and controls. Altered postprandial hormone secretion was mainly observed in constipated patients with prolonged oro-caecal transit time. In patients with slow transit constipation, fasting and postprandial secretion of proximal gut hormones apart from motilin is increased and of distal gut hormones decreased, especially in those with severely delayed intestinal transit.

Review article: gall‐bladder motor function in obesity

A number of epidemiological studies has established obesity as a risk factor for gallstone disease. More recently, studies have suggested a relationship between gallstone disease and the metabolic syndrome linked to central adiposity, whose cardinal feature is represented by hyperinsulinaemia. Studies on fasting gall-bladder volume in obese subjects show that this parameter correlates with weight, body mass index (BMI) and body surface area; however, this is also true for large-sized non-obese subjects. Gall-bladder volume also correlates with abdominal fat and with impaired glucose tolerance. In contrast to the well-established role of bile supersaturation in the pathogenesis of gallstones in obesity, data are controversial on whether gall-bladder motor function is defective in obese subjects. However, studies were heterogeneous for subjects' BMI, emptying stimulus, technique used and parameters assessed to evaluate gall-bladder motor function. Also, differences in baseline gall-bladder volume may lead to wide differences in bile 'washout' effect despite apparently similar percentage changes in volume or content. Although post-prandial plasma levels of cholecystokinin (CCK) are normal in obese subjects, there is some evidence that a sub-group of obese subjects could have decreased sensitivity to CCK, possibly mediated by hyperinsulinaemia. Further studies using standard physiological stimuli and controlling for glucose tolerance, fasting insulin levels and baseline gall-bladder volume are needed to establish the role of gall-bladder motor function in the pathogenesis of gallstone disease in obesity.

Effects of Intraluminal Trypsin and Bile on the Exocrine and Endocrine Pancreas After Pancreaticobiliary Diversion and Biliodigestive Shunt

Pancreaticobiliary diversion (PBD) and biliodigestive shunt (BDS) cause long-standing hypercholecystokininemia followed by pancreatic hyperplasia. These changes have been suggested to be due to the lack of intraluminal trypsin and bile, respectively, in the upper small intestine. The aim of these experiments was to study the effect of restoration of intraluminal trypsin and bile on plasma levels of cholecystokinin (CCK) and the changes found in exocrine and endocrine pancreas after PBD and BDS. Male Sprague-Dawley rats were used. PBD was done in 16 rats, eight of which had trypsin dissolved in 50 mM sodium bicarbonate (SB), and eight had SB only by gastric intubation twice daily. BDS was done in another 16 rats, eight of which had bile dissolved in SB, and eight had SB in a similar manner. Sham-operated rats had SB and served as controls. After 4 weeks, the rats were killed, and the concentrations of circulating CCK, gastrin, glucose, glucagon, and insulin were determined. The pancreas was removed, weighed, and analyzed for contents of water, protein, and DNA. In another study, PBD-operated rats got trypsin in varying dosages or trypsin and taurocholate in combination for 2 weeks before death. The concentrations of plasma CCK and glucagon were elevated after both PBD and BDS. PBD decreased the concentration of gastrin in plasma. PBD caused an increase of pancreatic weight and the contents of protein and DNA. Trypsin substitution to PBD-operated rats did not affect plasma CCK or glucagon levels, but the PBD-induced increases in weight and DNA content were counteracted by trypsin. Higher dosages of trypsin did not further influence the effects seen after PBD. Pancreatic weight and DNA content were increased after BDS. Bile administration completely abolished the increase in plasma CCK and glucagon, as well as the gain in pancreatic weight, and reduced the increase in pancreatic DNA. Substitution with bile to BDS-operated rats abolished the increase in the plasma levels of CCK and glucagon, as well as the trophic effects on the pancreas. Trypsin substitution to PBD-operated rats partly reversed the trophic effects on the pancreas but not the hormonal changes in plasma. Thus the trophic effects on the pancreas exerted by BDS seem to be dependent on the lack of bile in the upper small intestine, whereas the effects of PBD only partly are a consequence of the absence of intraluminal trypsin.

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.

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.

Gallbladder Emptying and Somatostatin and Cholecystokinin Plasma Levels in Celiac Disease

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. 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. 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. 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.

Hyperglycemia Reduces Pancreaticobiliary Secretion in Response to Modified Sham Feeding in Humans

Background/Aims: We have investigated the effect of acute hyperglycemia on pancreaticobiliary secretion and pancreatic polypeptide (PP) release. Methods: Duodenal outputs of bilirubin, trypsin, lipase, amylase and bicarbonate were measured using a recovery marker under basal conditions and in response to modified sham feeding (MSF) in 6 healthy subjects on two separate occasions: during normoglycemia and during acute hyperglycemia (15 mmol/l). Results: During hyperglycemia the basal pancreaticobiliary output was significantly (p < 0.05) reduced. During normoglycemia MSF significantly (p < 0.05) increased the output of bilirubin and pancreatic enzymes; during hyperglycemia only the output of pancreatic enzymes increased significantly (p < 0.05) over basal. During MSF the outputs of bilirubin (16 ± 4 vs. 4 ± 2 µmol/30 min), trypsin (26 ± 7 vs. 7 ± 4 U/30 min), lipase (36 ± 11 vs. 15 ± 6 kU/30 min), amylase (3.4 ± 0.7 vs. 1.4 ± 0.7 kU/30 min) and bicarbonate (0.8 ± 0.1 vs. 0.5 ± 0.1 mmol/30 min) were significantly (p < 0.05) reduced during hyperglycemia compared to normoglycemia. During hyperglycemia basal and MSF-stimulated PP levels were significantly (p < 0.05) reduced compared to normoglycemia. MSF did not significantly influence plasma cholecystokinin levels in both experiments. Conclusions: This study indicates (1) that the blood glucose levels affect basal and cephalic stimulated pancreaticobiliary secretion and (2) that the PP secretion during hyperglycemia is reduced, suggesting impaired vagal cholinergic activity during hyperglycemia.

Effect of a liquid meal given as a bolus into the jejunum on human pancreatic secretion.

Major features of pancreatic secretion stimulated by a meal depend on intestinal phase mechanisms. However, an intrajejunal (i.j.) meal infusion is widely used for the treatment of inflammatory pancreatic diseases when the resting of the gland is desired. This study was undertaken to compare the effects of an intragastric (i.g.) and an i.j. complete fluid (Lundh) test meal on pancreatic enzyme secretion. Eight men (mean age, 43 years; range, 31-48) free from pancreatic disease were studied. Pancreatic secretion was measured via a multiple-lumen tube by aspiration of the duodenal juice. After a fasting period, the Lundh test meal was placed in the stomach or the upper jejunum. After the i.g. administration of the test meal, the aspirated duodenal juice was reinfused into the jejunum. The effect of atropine infusion (0.5 microg/kg/h) on the pancreatic enzyme secretion was studied. The pancreatic amylase, trypsin, and lipase outputs were determined. The plasma levels of cholecystokinin (CCK) and of gastrin were measured by bioassay and radioimmunoassay, respectively. The trypsin, amylase, and lipase secretions increased significantly after either an i.g. or an i.j. test meal intake. The trypsin, amylase, and lipase outputs were significantly decreased during the i.j. perfusion as compared with i.g. administration. The gastrin levels increased significantly after i.g., but remained unchanged after i.j. administration. The CCK release attained its maximum 40 and 60 min after the i.g. and i.j. test meal, respectively. However, the CCK release was significantly lower during the i.j. administration as compared with i.g. perfusion. An atropine infusion significantly reduced the i.g. and i.j. test meal-stimulated enzyme outputs. An i.j.-administered meal stimulates the pancreatic enzyme secretion, but this effect is significantly lower than that which occurs on i.g. administration. The i.j. meal-stimulated secretion of pancreatic enzymes is subject to both cholinergic and peptidergic regulation. The deficiency of gastrin and the delayed and decreased CCK release are believed to account for the reduced enzyme output.

Colonic transit patterns and plasma cholecystokinin levels in children with recurrent abdominal pain.

Plasma cholecystokinin levels were measured in children with recurrent abdominal pain to investigate the relationship of plasma cholecystokinin levels with colonic transit patterns and clinical symptoms. Subjects consisted of 120 children (mean age 9.6 +/- 2.6 years) for whom colonic transit study had also been done. Plasma cholecystokinin levels were 79.2 +/- 58.7 pg/mL in children with colonic inertia, 70.7 +/- 47.0 pg/mL in hindgut dysfunction, 57.4 +/- 53.1 pg/mL in pelvic outlet obstruction, and 67.6 +/- 47.9 pg/mL in normal colonic transit. These data showed that there was a tendency of increasing plasma cholecystokinin levels in children with proximal colon transit delay, although there was no significant difference among four groups. Plasma cholecystokinin levels in children of 10 years of age and under (54.5 +/- 40.4 pg/mL) were significantly lower (p = 0.01) than in children over 10 years (79.1 +/- 59.8 pg/mL). Plasma cholecystokinin levels based on colonic transit patterns, however, were not significantly different between the two age groups. There was no significant difference in plasma cholecystokinin levels between groups based on defecation frequency per week, presence of defecation pain, symptoms of milk intolerance, or the presence of emotional stress. These results suggested that there was a tendency of increasing plasma cholecystokinin levels in the younger age group and in children with delay in proximal colonic transit, but further study is required in relation to plasma cholecystokinin levels based on colonic transit patterns in a large number of patients.

Plasma somatostatin and cholecystokinin levels in preterm infants during kangaroo care with and without nasogastric tubefeeding

Plasma somatostatin and cholecystokinin levels in preterm infants during kangaroo care with and without nasogastric tubefeeding

Plasma somatostatin and cholecystokinin levels in response to feeding in preterm infants.

The functions of the gut are modulated by the autonomic nervous system and gut peptides, such as somatostatin and cholecystokinin, which have opposite functions. This study reports plasma somatostatin and cholecystokinin levels in response to feeding in preterm infants. In 76 infants--gestational age 23 to 36 weeks, birth weight 460 to 2867 g--blood samples were taken on day 1 before the first meal in life, and 30 minutes after the end of the meal. Samples were again taken on days 3 and 4. The infants were fed human milk by nasogastric tube, by breast, or by bottle. In 10 additional infants, (gestational age 27-36 weeks) who were studied at a median postnatal age of 15 days, the response of the peptides to breast-feeding was compared with that of tube-feeding. Plasma somatostatin and cholecystokinin were analyzed by specific radioimmunoassays. On day 1, the median plasma somatostatin level increased after feeding in small-for-gestational-age infants but not in appropriate-for-gestational-age infants. On days 3 and 4, the somatostatin level decreased in infants with a gestational age of 32 weeks or more. On day 1, plasma cholecystokinin levels increased in infants with a gestational age of 32 weeks or more: The response was more pronounced in small-for-gestational-age infants. On days 3 and 4, plasma cholecystokinin levels increased only in breast-feeding infants. In the 10 infants fed by breast and by tube, plasma cholecystokinin levels increased after breast-feeding and tended to increase after tube-feeding. The plasma somatostatin levels were unaffected after feeding. Plasma somatostatin and cholecystokinin increased after feeding in small-for-gestational-age infants on day 1. On days 3 and 4, the responses to feeding seemed to be dependent on the infant's gestational age. Breast-feeding enhanced the release of cholecystokinin but not that of somatostatin.

Adaptation of the human pancreas to inhibition of luminal proteolytic activity

Background & Aims: Feedback regulation of pancreatic enzyme secretion is well established in animals, and their pancreases are able to adapt to intraduodenal inhibition of pancreatic enzymes by proteinase inhibitors such as Camostate (FOY-305; Schwarz GmbH, Monheim, Germany). In this study, we addressed whether similar adaptive changes occur in the human pancreas after 4 weeks of 2 g/day Camostate application. Methods: Before, at the end of, and 2 weeks after 4-week Camostate treatment (four times 500 mg daily), pancreatic changes were analyzed with the use of a secretin-cerulein test, a test-meal stimulation, cholecystokinin plasma measurement, and standardized ultrasonographic investigations of the pancreas. Results: Duodenal trypsin output after secretion stimulation was significantly increased (+44%; P < 0.01) and duodenal bicarbonate output decreased 22% ( P < 0.05) after 4 weeks of Camostate application. The size of the pancreatic head (vertical) increased 8% ( P < 0.05) at week 4 and decreased to pretreatment values 2 weeks after treatment (week 6). The other three diameters measured (head oblique, body, and tail) showed a similar pattern. Stimulated cholecystokinin plasma levels 15 minutes after application of a standard test meal increased 62% ( P < 0.05). Conclusions: The human pancreas adapts to oral application of the proteinase inhibitor Camostate. These findings support the theory that feedback control of the exocrine pancreas operates in humans. GASTROENTEROLOGY 1998;115:388-396

Inhibition of gastric emptying and intestinal transit by amphetamine through a mechanism involving an increased secretion of CCK in male rats.

1. The effect of amphetamine on gastrointestinal (GI) transit and the plasma levels of cholecystokinin (CCK) were studied in male rats. 2. Gastric emptying was inhibited both acutely and chronically by the administration of amphetamine. GI transit was decreased by the acute administration of amphetamine but not affected by the chronic administration of amphetamine. 3. Plasma CCK levels were increased dose-dependently by amphetamine. 4. Proglumide, a CCK receptor antagonist, prevented amphetamine-induced inhibition of gastric emptying and the decrease in GI transit in male rats. 5. The selective CCK(A) receptor antagonist, lorglumide, dose-dependently attenuated the amphetamine-induced inhibition of gastric emptying in male rats. In contrast, the selective CCK(B) receptor antagonist, PD 135,158, did not reverse the effect of amphetamine on gastric emptying. 6. Both lorglumide and PD 135,158 reversed the inhibitory effect of amphetamine on GI transit in male rats. 7. These results suggest that amphetamine-induced inhibition of gastric emptying and intestinal transit is due in part to a mechanism associated with the hypersecretion of endogenous CCK.

Admission plasma cholecystokinin levels are low both in acute alcoholic and biliary pancreatitis

Background Recent studies have shown that cholecystokinin (CCK) agonist, cerulein can induce acute pancreatitis in animals. The role of CCK in the induction of acute pancreatitis in man is unclear. We investigated admission plasma CCK levels in alcoholic and biliary pancreatitis. Method Plasma CCK concentrations were determined by a specific and sensitive radioimmunoassey using CCK antiserum (Euro-Diagnostica, Malmti, Sweden) in 35 patients with acute alcoholic pancreatitis, in 27 patients with acute biliary pancreatitis, in 34 patients with non-pancreatic acute abdominal pain and in 43 healthy subjects. The mean time from the first symptoms to the plasma sample was 31 ( ± 3.7) hours in alcoholic pancreatitis patients and 25 ( ± 5.1) hours in biliary pancreatitis patients. Normal fasting level of CCK is _ 1.12 pmol/1) significantly more often in non-pancreatic acute abdominal pain patients than in alcoholic pancreatitis patients (12/34 vs 0/35, p=0.00006) or biliary pancreatitis patients (12/34 vs 1/27, p=0.002) and also significantly more often in healthy subjects than in alcoholic pancreatitis patients (17/43 vs 0/35, p=0.000007) or biliary pancreatitis patients (17/43 vs 1/27, p=0.0005). Conclusion Basal plasma CCK concentrations are significantly decreased in acute alcoholic and biliary pancreatitis early in the course of the disease.

CCK-, secretin-, and cholinergic-independent pancreatic fluid hypersecretion in protease inhibitor-treated rats.

Plasma cholecystokinin (CCK) levels in fed rats increased from 2.59 +/- 0.13 pmol/l to the peak of 27.6 +/- 4.1 pmol/l at 1 h after a single oral administration of synthetic protease inhibitor (PI; ethyl N-allyl-N-[(E)-2-methyl-3-[4-(4-amidino-phenoxycarbonyl)phenyl] propenoyl] amino acetate methansulfonate; 20 mg/kg body wt), but then returned to the preloading value at 12 h after administration. The pancreatic fluid secretion, rich in chloride but poor in bicarbonate, was significantly elevated at 6-12 h postfeeding (100.9 +/- 8.2 vs. 27.3 +/- 2.3 microliters/30 min in control rats, P < 0.01). Loxiglumide (50 mg.kg body wt-1.h-1), atropine (100 micrograms.kg body wt-1.h-1), or antisecretin serum (100 microliters/rat) at 12 h postfeeding did not modify the fluid hypersecretion. Loxiglumide, when given together with PI, completely abolished fluid hypersecretion, but it could not inhibit hypersecretion when applied 3 h after PI treatment. Labeling with 5-bromo-2'-deoxyuridine showed active proliferation of acinar cells at 3 h after PI treatment (3.56 +/- 0.29% vs. 0.46 +/- 0.08% in control, P < 0.001), but not in rats given loxiglumide together with PI. In rats that fasted from 12 h before to 12 h after PI feeding, neither pancreatic fluid hypersecretion nor active proliferation of acinar cells was observed. These results suggest that pancreatic fluid hypersecretion in fed rats at 6-12 h after PI treatment is caused not by CCK-, secretin-, or cholinergic-dependent mechanisms but probably by acinar cell proliferation.

Plasma somatostatin and cholecystokinin levels in preterm infants during kangaroo care with and without nasogastric tube-feeding.

To analyze the influence of kangaroo care (KC) with and without nasogastric tube-feeding (NGTF) on plasma cholecystokinin (CCK) and somatostatin (SS) levels in preterm infants and in their parents. Eighteen infants, median (range) gestational age 28 wks (24-34 wks) and birth weight 1230 g (766-2660 g) received KC for > or = 60 min at a median age of 3 days. In infants, blood samples were taken before KC and at 5, 30 and > or = 60 minutes of KC and from the parents (n = 15) before and at > or = 60 minutes of KC. Eight infants receiving KC and 67 infants not receiving KC were fed by nasogastric tube. Blood samples were taken before and 30 min after the end of feeding. All blood samples were analyzed by specific SS and CCK radioimmunoassays. In infants, the median plasma cholecystokinin level decreased from 10.3 to 9.0 pmol/l (p < 0.05) during KC without feeding. Plasma SS did not change. Plasma CCK levels increased from 10.1 to 22.3 pmol/l (p = 0.028) after NGTF during KC and were unchanged after NGTF without KC. Plasma somatostatin levels were unchanged after NGTF in both groups. In parents, plasma somatostatin levels and cholecystokinin levels did not change during KC. In infants, plasma cholecystokinin, but not somatostatin levels, decreased during KC. Plasma CCK levels increased after NGTF only in combination with KC. Plasma SS levels were unchanged. In parents, plasma somatostatin and cholecystokinin levels were not influenced by KC.

Hydrolysis of dietary fat by pancreatic lipase stimulates cholecystokinin release

Background & Aims: The hypothesis that cholecystokinin release requires adequate dietary fat digestion in the small intestine was investigated in 10 healthy volunteers, and the consequences of reduced fat hydrolysis on pancreaticobiliary secretions were assessed. Methods: Fat hydrolysis was inhibited by intraduodenal perfusion of tetrahydrolipstatin, an irreversible lipase inhibitor. An oil emulsion containing 0, 30, 60, or 120 mg tetrahydrolipstatin was perfused. After a 40-minute basal period, a test meal was eaten to stimulate cholecystokinin release and pancreaticobiliary responses. Results: In the control without tetrahydrolipstatin, lipase output increased threefold with meal ingestion and remained doubled for 4 hours. At the ligament of Treitz, free fatty acid concentration averaged 60% of total fatty acids. Increasing doses of tetrahydrolipstatin induced a dose-dependent inhibition of duodenal lipase activity ( P < 0.01); 120 mg tetrahydrolipstatin eliminated the postprandial lipase peak activity, free fatty acid levels decreased to <5% of total fatty acids, and plasma cholecystokinin levels were suppressed by 77% ( P < 0.01). Amylase and trypsin outputs were reduced by 77% and 59%, respectively, and bilirubin secretion was virtually abolished ( P < 0.01). Conclusions: These findings show that tetrahydrolipstatin prevents triglyceride hydrolysis and that plasma cholecystokinin release, gallbladder emptying, and pancreatic enzyme secretion require adequate triglyceride digestion. These data also support the concept of negative feedback regulation of cholecystokinin secretion. GASTROENTEROLOGY 1998;114:123-129

Development of a Preferential Relationship With the Mother by the Newborn Lamb: Importance of the Sucking Activity

Lambs develop a preferential relationship with their mothers within 24 h after birth. In a first experiment, we attempted to determine whether neonatal sucking was a potent reinforcer in the establishment of this preference by temporarily covering the udders of ewes after parturition. Lambs were assigned to one of three treatments: they had free access to the udder (group 1) or were prevented from sucking either between birth and 6 h afterward (group 2) or between 12 and 18 h after birth (group 3). Measurements of cholecystokinin plasma levels at birth and at 6 and 18 h showed that all lambs ingested some colostrum when the udder was made accessible. When tested in a two-choice test situation at 24 h of age, lambs from group 1 spent significantly more time near their mothers than near the alien ewes, those from group 2 did not show any discrimination, and lambs from group 3 clearly preferred the alien ewes. At 2 days of age, lambs from groups 1 and 3 showed a strong preference for their mothers, whereas those from group 2 still displayed no preference. In a second experiment, we attempted to determine whether sucking also had a reinforcing value in the maintenance of this preference. Lambs were assigned to one of three treatments: they had free access to the udder (group 1) or were prevented from sucking for 6 h either at birth (group 2) or at the age of 3 days (group 3). Lambs from group 2 did not discriminate between their own and alien dams when tested at 24 h of age, unlike those of groups 1 and 3. When a second test was performed at 4 days of age, all the lambs showed a strong preference for their dams. We concluded that sucking has strong rewarding properties in the establishment of a preferential relationship with the mother by the lamb. On the other hand, the maintenance of this preference does not rely on sucking as strongly.

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.