In vitro gastric emptying characteristics of konjac glucomannan with different viscosity and its effects on appetite regulation.

Konjac glucomannan (KGM) is associated with the satiety-enhancing property by imparting the food matrix with high viscosity. In the present study, rheology tests on KGM sol with different viscosities were conducted to understand its flow behavior as they presented in the mouth and stomach, and the in vitro gastric emptying characteristics of KGM were examined with a human gastric simulator. Then, their effects on subjective appetite, glycemia, and appetite-related hormones (insulin, GLP-1, PYY3-36, CCK-8, ghrelin) response were investigated by conducting a randomized, single-blind, crossover trial in 22 healthy adults (11 female and 11 male, mean age (years): 23.2 ± 2.0, BMI (kg m-2): 20.6 ± 2.1). The blood samples and ratings for subjective appetite were collected at regular time intervals after the subjects were fed with four test breakfasts (one control treatment and three experimental treatments) on four different days. An ad libitum lunch was provided to the subjects once they consumed the breakfasts and their food intake was recorded. As the viscosity increased, the gastric emptying rate was delayed despite a large part of the chyme viscosity lost during digestion. The satiating capacity of the test breakfast was significantly enhanced as its viscosity increased, the and subjects' sensation for hunger, fullness, desire-to-eat, and prospective food consumption differed significantly (p = 0.006, 0.000, 0.002, and 0.001, respectively) between the treatments. The secretion of glycemia and satiety-related hormones were beneficially modulated by the increased viscosity of the test meal but a small decrease in the ad libitum food intake was observed after the intervention of the viscous test breakfasts. Overall, elevating the meal viscosity moderately by using KGM could contribute to combating the challenge of hunger for people in the bodyweight management.

Cholecystokinin octapeptide reduces myocardial fibrosis and improves cardiac remodeling in post myocardial infarction rats.

BACKGROUND/AIMS: Myocardial infarction (MI) increases myocardial fibrosis (MF) and subsequent cardiac remodeling. Cholecystokinin octapeptide (CCK-8) is expressed in cardiomyocytes and plays an important role in cardiovascular regulation. In this study, we intend to use a rat model of myocardial infarction to evaluate the effects of CCK-8 on myocardial fibrosis and cardiac remodeling. METHODS: Male Sprague-Dawley rats were separated into 3 groups: sham operation, MI + NaCl, and MI + CCK-8. All rats were subjected to left coronary artery ligation to induce MI or sham operation and then treated with CCK-8 or saline for 28 days. After 4 weeks, echocardiography was performed to assess cardiac function and myocardial fibrosis was evaluated using H&E and Masson's Trichrome-stained sections. The levels of BNP, CCK-8 in the plasma of all rats were detected by ELISA; RNA sequencing (RNA-seq) analysis was also adapted to detect differentially expressed genes in myocardial tissues of each group. Myocardial expression of fibrosis markers was analyzed by western blotting, immunohistochemistry and qRT-PCR. RESULTS: CCK-8 was demonstrated to improve left ventricular function and results of H&E staining, Masson's trichrome staining, immunohistochemistry and western blotting showed that CCK-8 attenuated MF. Gene expression profiles of the left ventricles were analysed by RNA-seq and validated by qRT-PCR. Cardiac fibrosis genes were downregulated by CCK-8 in the left ventricle. SIGNIFICANCE: CCK-8 can alleviate fibrosis in the noninfarcted regions and delay the left ventricular remodeling and the progress of heart failure in a MI rat model.

Appetite responses to high-fat diets rich in mono-unsaturated versus poly-unsaturated fats.

BACKGROUND: Modifying the type of dietary fat consumed may impact appetite, therefore having implications in weight management. OBJECTIVE: To test the effects of a 5-day, high-fat diet rich in poly-unsaturated fatty acids (PUFAs) and a diet rich in mono-unsaturated fatty acids (MUFAs) on markers of appetite. METHODS: Fifteen normal weight men participated in a randomized cross-over design with two controlled feeding trials (3d lead-in diet, pre-diet visit, 5d PUFA- or MUFA-rich diet, post-diet visit). The 5d diets (50% fat) were rich in either PUFA (25% of energy) or MUFA (25% of energy). At pre- and post-diet visits, subjects consumed breakfast and lunch test meals, rich in the FA corresponding to the 5-day diet. Fasting and postprandial subjective ratings of appetite were determined and blood draws were performed for 4h after each meal to determine changes in appetite hormones. An ad libitum buffet meal was given at the end of pre- and post-diet visits. RESULTS: Acutely, at the pre-diet visit, the PUFA-rich meal resulted in lower ghrelin (hunger hormone) (iAUC: -350.85 ±â€¯60.70 vs. -233.16 ±â€¯61.42 pg/ml/8h, for PUFA vs. MUFA, respectively; p < 0.05) and higher CCK (satiation hormone) (iAUC: 238.09 ±â€¯46.07 vs. 196.84 ±â€¯33.92 pM/8h, for PUFA vs. MUFA, respectively; p < 0.05). No other acute meal challenge differences were found. The 5d high PUFA diet resulted in lower hunger ratings (iAUC: -172.06 ±â€¯40.59 vs. -274.46 ±â€¯41.47 mm/8h, for pre-to post-diet, respectively; p < 0.05). However, energy intake, ratings of fullness, or PYY did not change from pre-to post-diet for either MUFA or PUFA, and no other changes were observed with the MUFA diet. CONCLUSIONS: Acutely, a PUFA-rich meal results in ghrelin suppression and higher CCK. After a 5-day high-fat diet, PUFAs suppressed postprandial hunger while MUFAs did not change any measures of appetite.

Effect of resistant wheat starch on subjective appetite and food intake in healthy adults.

OBJECTIVE: The aim of this study was to determine the effect of replacing standard wheat flour (SWF) with resistant wheat starch (RWS) on markers of appetite and food intake in healthy adults. METHODS: A randomized, single-blind, crossover study was conducted with 27 healthy adults (ages 23 ± 2 y with a body mass index of 23.0 ± 3.0 kg/m2). After an overnight fast, muffins that contained only SWF or muffins in which 40% of the SWF was replaced with RWS were consumed as part of the breakfast meal. Appetite questionnaires and plasma samples were collected before the test meal and at 10 time points after meal consumption. An ad libitum meal was provided 240 min after breakfast, and the amount eaten was recorded. Food intake was recorded over the remainder of the day using a diet diary, and appetite was measured hourly using appetite questionnaires. Plasma was assayed to measure biomarkers of satiety and glycemia. RESULTS: Replacing SWF with RWS had no effect on subjective appetite or energy intake at the lunch meal (P > 0.05). Total daily energy intake (including the breakfast meal) was reduced by 179 kcal when participants consumed the RWS muffins (P = 0.05). Replacing SWF with RWS reduced plasma insulin (P < 0.05) but had no effect on plasma glucose, cholecystokinin, glucagon-like peptide-1, or peptide YY3-36 concentration (P > 0.05). CONCLUSIONS: These results indicate that replacing SWF with RWS decreases plasma insulin concentration and reduces energy intake over a 24-h period.

Postprandial profiles of CCK after high fat and high carbohydrate meals and the relationship to satiety in humans.

CONTEXT: CCK is understood to play a major role in appetite regulation. Difficulties in measuring CCK have limited the potential to assess its profile in relation to food-induced satiety. Improvements in methodology and progress in theoretical understanding of satiety/satiation make it timely for this to be revisited. OBJECTIVE: First, examine how physiologically relevant postprandial CCK8/33(s) profiles are influenced by fat (HF) or carbohydrate (HCHO) meals. Second, to examine relationships between postprandial CCK and profiles of satiety (hunger/fullness) and satiation (meal size). PARTICIPANTS AND DESIGN: Sixteen overweight/obese adults (11 females/5 males) participated in a randomised-crossover study (46 years, 29.8 kg/m(2)) in a university research centre. Plasma was collected preprandially and for 180 min postprandially. Simultaneously, ratings of hunger/fullness were tracked for 180 min before an ad libitum lunch was provided. RESULTS: CCK8/33(s) levels increased more rapidly and reached a higher peak following HF compared to HCHO breakfast (F(1,15)=14.737, p<0.01). Profiles of hunger/fullness did not differ between conditions (F(1,15)=0.505, p=0.488; F(1,15)=2.277, p=0.152). There was no difference in energy intake from the ad libitum meal (HF-3958 versus HCHO-3925 kJ; t(14)=0.201, p=0.844). CCK8/33(s) profiles were not associated with subjective appetite during early and late phases of satiety; nor was there an association between CCK8/33(s) and meal size. CONCLUSIONS: These results demonstrate CCK levels were higher after HF meal compared to HCHO isocaloric meal. There was no association between CCK levels and intensity of satiety, or with meal size. Under these circumstances, CCK does not appear to play a unique independent role in satiety/satiation. CCK probably acts in conjunction with other peptides and the action of the stomach.

Roles of sphincter of Oddi motility and serum vasoactive intestinal peptide, gastrin and cholecystokinin octapeptide.

AIM: To investigate roles of sphincter of Oddi (SO) motility played in pigment gallbladder stone formation in model of guinea pigs. METHODS: Thirty-four adult male Hartley guinea pigs were divided randomly into two groups: the control group and pigment stone group. The pigment stone group was divided into 4 subgroups with 6 guinea pigs each according to time of sacrifice, and were fed a pigment lithogenic diet and sacrificed after 3, 6, 9 and 12 wk. SO manometry and recording of myoelectric activity of the guinea pigs were obtained by multifunctional physiograph at each stage. Serum vasoactive intestinal peptide (VIP), gastrin and cholecystokinin octapeptide (CCK-8) were detected at each stage in the process of pigment gallbladder stone formation by enzyme-linked immunosorbent assay. RESULTS: The incidence of pigment gallstone formation was 0%, 0%, 16.7% and 66.7% in the 3-, 6-, 9- and 12-wk group, respectively. The frequency of myoelectric activity decreased in the 3-wk group. The amplitude of myoelectric activity had a tendency to decrease but not significantly. The frequency of the SO decreased significantly in the 9-wk group. The SO basal pressure and common bile duct pressure increased in the 12-wk group (25.19 ± 7.77 mmHg vs 40.56 ± 11.81 mmHg, 22.35 ± 7.60 mmHg vs 38.51 ± 11.57 mmHg, P < 0.05). Serum VIP was significantly elevated in the 6- and 12-wk groups and serum CCK-8 was decreased significantly in the 12-wk group. CONCLUSION: Pigment gallstone-causing diet may induce SO dysfunction. The tension of the SO increased. The disturbance in SO motility may play a role in pigment gallstone formation, and changes in serum VIP and CCK-8 may be important causes of SO dysfunction.

[Blood serum cholecystokinin and clinical-functional variability of biliary pathology].

RESULTS: Basal and stimulated serum CCK concentrations were not statistically significant differences (p > 0.05) with the control group in patients studied in the whole and in patients subgroups, formed by the diagnosis of biliary pathology and the character of gallbladder emptying. Increased stimulated CCK concentration was found in patients with symptomatic variants. Reduce of serum-cholecystokinin concentration growth (ACCK) after intake of Sorbitol was revealed in subgroup of patients with low-symptom variant. Reduced sensitivity of the gallbladder to CCK was observed in subgroups of patients with gallbladder hypokinetic dyskinesia and one with symptomatic variant of biliary pathology. CONCLUSION: The sensitivity of the gallbladder neuromuscular apparatus to CCK is associated with clinical and functional variability of the biliary pathology.

Circulating GLP-1 and CCK-8 reduce food intake by capsaicin-insensitive, nonvagal mechanisms.

Previous reports suggest that glucagon-like peptide (GLP-1), a peptide secreted from the distal small intestine, is an endocrine satiation signal. Nevertheless, there are conflicting reports regarding the site where circulating GLP-1 acts to reduce food intake. To test the hypothesis that vagal afferents are necessary for reduction of food intake by circulating GLP-1, we measured intake of 15% sucrose during intravenous GLP-1 infusion in intact, vagotomized, and capsaicin-treated rats. We also measured sucrose intake during intravenous infusion of cholecystokinin, a peptide known to reduce food intake via abdominal vagal afferents. We found that reduction of intake by GLP-1 was not diminished by capsaicin treatment or vagotomy. In fact, reduction of sucrose intake by our highest GLP-1 dose was enhanced in vagotomized and capsaicin-treated rats. Intravenous GLP-1 induced comparable increases of hindbrain c-Fos immunoreactivity in intact, capsaicin-treated, and vagotomized rats. Plasma concentrations of active GLP-1 in capsaicin-treated rats did not differ from those of controls during the intravenous infusions. Finally, capsaicin treatment was not associated with altered GLP-1R mRNA in the brain, but nodose ganglia GLP-1R mRNA was significantly reduced in capsaicin-treated rats. Although reduction of food intake by intraperitoneal cholecystokinin was abolished in vagotomized and capsaicin-treated rats, reduction of intake by intravenous cholecystokinin was only partially attenuated. These results indicate that vagal or capsaicin-sensitive neurons are not necessary for reduction of food intake by circulating (endocrine) GLP-1, or cholecystokinin. Vagal participation in satiation by these peptides may be limited to paracrine effects exerted near the sites of their secretion.

[Effect of chai qin cheng qi decoction on serum CCK-8 and calcium overload of pancreatic acinar in mice with acute pancreatitis].

OBJECTIVE: To investigate the effect of Chai Qin Cheng Qi decoction (CQCQD) on serum cholecystokinin-8 (CCK-8) and calcium overload of pancreatic acinar cells in acute pancreatitis (AP) mice. METHODS: Twenty four mice were randomly divided into control group, AP group, CQCQD group and siRNA group, each comprising 6 mice. AP mouse model was induced by intraperitoneal injection of 8% L-arginine in a dose of 4 g/kg. The AP mice in the CQCQD group were fed with 0.4 mL/100 g of Chai Qin Cheng Qi solution once every two hours. The AP mice in the siRNA group were injected intraperitoneally with CCK-siRNA in a dose of 0.88 mg/kg. The changes of serum CCK-8 and calcium concentrations in the pancreatic acinar cells and pancreatic pathology were observed 6 hours after the interventions. RESULTS: The serum CCK-8 [(3764.3 +/- 369.2) ng/mL], calcium fluorescence intensity (34.8 +/- 27.1) of pancreatic acinar cells and pancreas pathology scores (6.2 +/- 1.1) of the AP mice were significantly greater (P < 0.05) than those in the control group [(1253.5 +/- 39.5) ng/mL, 5.2 +/- 2.3, 2.8 +/- 0.4], CQCQD group [(1230.5 +/- 46.1) ng/mL, 9.6 +/- 1.6, 3.8 +/- 0.8, 4.1 +/- 0.5] and siRNA group[(1702.3 +/- 598.3) ng/mL, 7.6 +/- 2.0]. Serum CCK-8 was positively correlated with intracellular calcium concentrations (r = 0.793, P = 0.021) in pancreatic acinar cells and pancreas pathology scores (r = 0.847, P = 0.000). CONCLUSION: Acute pancreatitis in mice induced by L-arginine is associated with calcium overload in pancreatic acinar cells induced by increased serum CCK-8. CQCQD can reduce serum levels of CCK-8, alleviate calcium overload in pancreatic acinar cells, and reduce pancreas pathological changes in AP mice.

Effect of viscosity on appetite and gastro-intestinal hormones.

In previous studies we showed that higher viscosity resulted in lower ad libitum intake and that eating rate is an important factor. In this study we aimed to explore the effect of viscosity on the gastro-intestinal hormones ghrelin, CCK-8 and GLP-1. Thirty-two subjects (22+/-2 y, BMI 21.9+/-2.2 kg/m(2)) participated in this cross-over study. Subjects received a fixed amount of a chocolate flavored milk-based liquid or semi-solid product similar in energy density and macronutrient composition. Before intake and 15, 30, 60 and 90 min thereafter, appetite was rated and blood was drawn to determine glucose, CCK-8, active ghrelin, desacyl ghrelin and GLP-1 concentrations. After the last blood withdrawal, subjects were offered a chocolate cake meal to consume ad libitum. In the appetite ratings we observed a small effect showing that the semi-solid product is apparently considered as more satisfying than the liquid. There was a significant product effect for fullness (p 0.03), desire to eat (p 0.04), appetite something sweet (p 0.002) and prospective consumption (p 0.0009). We observed no clear effect of viscosity on gastro-intestinal hormones. Only for desacyl ghrelin there was a significant product effect (p 0.004). Concentrations were consistently higher after intake of the semi-solid product. Ad libitum intake of the chocolate cake was 102+/-55 g after the liquid and 96+/-46 g after the semi-solid product (ns). The results of our study show a similar response of the gastro-intestinal hormones CCK-8, ghrelin and GLP-1 after a fixed preload of a liquid and semi-solid product similar in energy- and macronutrient composition.

Inhibitory effects of somatostatin on cholecystokinin octapeptide induced bile regurgitation under stress: ionic and molecular mechanisms.

OBJECTIVE: To investigate the possible effects and related ionic and molecular mechanisms of changes of plasma cholecystokinin octapeptide and somatostatin on stress-induced bile regurgitation in rats. METHODS: In forty healthy adult rats, changes of plasma cholecystokinin octapeptide, somatostatin and intragastric bile concentration under stressful condition were respectively measured by specific radioimmunoassay methods. Contractile responses of gastric antral smooth strips isolated from healthy adult rats were recorded by polyphysiograph. Immunoprecipitation was used to determine the regulatory effect of protein kinase C on regulating the phosphorylation of type 3 inositol 1,4,5-triphosphate receptor (InsP3R3) in gastric smooth muscle cells. Changes of intracellular calcium fluorescence intensity of smooth muscle cells presented as intracellular calcium ([Ca2+]i) were analyzed under laser scanning confocal microscopy and L-type voltage-dependent calcium currents of smooth muscle cells were recorded by patch-clamp techniques. RESULTS: Compared with the normal control group, plasma cholecystokinin octapeptide and gastric bile concentration of each stress group significantly increased during the stress, while adverse effect was obtained in plasma somatostatin, which decreased from the beginning of the stress and attained the minimum nearly at the same time when the plasma cholecystokinin octapeptide concentration reached the maximum. Respective addition of cholecystokinin octapeptide and somatostatin with increasing concentrations caused rapid, sustained, concentration-dependent increase and decrease in muscle contraction of gastric antral strips, and cholecystokinin octapeptide that increased the contractile response could be blocked by respective administration of nifedipine and somatostatin significantly. Similar results were obtained in the changes of calcium fluorescence intensity and calcium currents of smooth muscle cells. Pretreatment with somatostatin significantly increased cholecystokinin octapeptide-increased phosphorylation of InsP3R3 in smooth muscle cells. CONCLUSIONS: Gastric mucosal damage induced by bile regurgitation is closely connected with gastric antral dysmotility evoked by the changes of cholecystokinin octapeptide and somatostatin under stressful condition. Cholecystokinin octapeptide-intensified contraction depends on the release of intracellular calcium stores and the influx of extracellular calcium via L-type voltage-dependent calcium channels, while this excitatory effect of cholecystokinin octapeptide could be blocked by somatostatin, suggesting that both of the two peptides play important roles in the regulation of gastric motility.

Subclinical exocrine pancreatic dysfunction resulting from decreased cholecystokinin secretion in the presence of intestinal villous atrophy.

UNLABELLED: The aim of this study was to evaluate the concept that pancreatic dysfunction in patients having gluten sensitivity (celiac disease [CD]) or cow's milk protein enteropathy (CMPE) may result from the lack of pancreatic enzyme stimulation in the absence or decrease of cholecystokinin (CCK) secretion caused by villous atrophy. PATIENTS AND METHODS: The following parameters were measured: plasma CCK in response to a fatty meal and human pancreatic fecal elastase in 24 patients with CD while on gluten-free diet and after gluten provocation and in 12 patients with CMPE at diagnosis and after a 6-month period of cow's milk-free diet. Intestinal mucosa morphology was examined by small bowel biopsy. Sixty-three controls having no organic gastrointestinal problems were investigated once at the time of diagnostic evaluation. RESULTS: Fasting CCK, obtained at a time when patients with CD or CMPE had normal intestinal mucosa, was significantly different from postprandial and comparable to that of the control group. Fasting CCK obtained from patients with villous atrophy was also statistically different, but not significantly, from the postprandial. Fasting and postprandial plasma CCK and fecal pancreatic elastase values from patients having normal intestinal mucosa were significantly higher than those obtained from patients with villous atrophy. Significant correlation of intestinal mucosa morphology and CCK with fecal elastase concentration was documented. CONCLUSION: Exocrine pancreatic dysfunction in individuals having villous atrophy may be the consequence of decreased CCK secretion. Cholecystokinin and pancreatic secretion is restored to normal, with intestinal mucosa regeneration.

[The effect and mechanism of cholecystokinin octapeptide induced-gastric dysmotility on bile regurgitation during stress].

OBJECTIVE: To illustrate the existence of bile regurgitation under stress condition, and explore the possible effects and related mechanism of changes of cholecystokinin octapeptide (CCK-8) on stress-induced bile regurgitation in rats. METHODS: (1) Changes in plasma CCK-8 and gastric bile concentration were measured by using radioimmunoassay while simultaneously calculating gastric ulcer index and intragastric pH; (2) Each isolated gastric strips were suspended in a tissue chamber to record the contractile responses by polyphysiograph; (3) The responsiveness of gastric smooth muscle cells (SMCs) to sulfated cholecystokinin octapeptide (CCK-8S) were examined using fura-2-loaded microfluorimetric measurement of intracellular calcium concentration ([Ca(2+)] i); (4) The current of L-type calcium channels (I(CaL)) of SMCs were recorded by patch-clamp techniques. RESULTS: (1) Compared with the normal control, plasma CCK-8 [from (2.23 +/- 0.88) pmol/L to (10.80 +/- 3.82) pmol/L] and gastric bile concentration [from (37.93 +/- 23.76) micromol/L to (1316.00 +/- 197.36) micromol/L] significantly increased during the stress (P < 0.01) and both simultaneously reached the peak at the time point of 2 h after stress; ulcer index (from 0.62 +/- 0.23 to 32.01 +/- 16.11) and intragastric pH (from 1.06 +/- 1.20 to 5.29 +/- 1.25) apparently increased (P < 0.01); (2) Significant changes to CCK-8S were found in the mean contractile amplitude and frequency of circular muscle and longitudinal muscle of gastric antrum and pylorus; (3) CCK-8S-evoked significant increase in [Ca(2+)] i [from (65.8 +/- 7.4) nmol/L to (472.1 +/- 35.6) nmol/L, P < 0.01] could be suppressed by CCK-A receptor antagonist; whereas a small but significant increases were still elicited by CCK-8S under condition of the removal of extracellular calcium; (4) CCK-8S-intensified calcium current I(Ca-L) [from (-56.42 +/- 6.57) pA to (-88.54 +/- 5.71) pA, P < 0.01)] apparently inhibited by respective administration of nifedipine, Ca(2+)-ATPase inhibitors or calcium dependent chloride channel blocker (P < 0.01). CONCLUSIONS: Gastric mucosal damage induced by bile regurgitation is closely connected with gastric antrum and pylorus dysmotility evoked by CCK-8 during the stress. CCK-8S-evoked [Ca(2+)] i increase in gastric antrum and pylorus SMC depends on the release of intracellular calcium stores which activates L-type voltage-dependent calcium channels through the activation of calcium dependent chloride channels.

Cholecystokinin octapeptide (CCK-8) concentration in plasma is not affected in functional abdominal pain in children.

PURPOSE: Cholecystokinin regulates gut motility and visceral sensation. The aim of the study was to determine the diagnostic value of plasma cholecystokinin octapeptide (CCK-8) concentration in children with functional abdominal pain (FAP). MATERIAL AND METHODS: Fifty-two children (33 girls and 19 boys) aged 6-17 years with chronic abdominal pain were included in this study. On the basis of clinical data, results of endoscopy and Criteria for Functional Disorders the patients were divided into three groups: group 1--functional dyspepsia (FD), group 2--irritable bowel syndrome (IBS), group 3--non-specific FAP. The control group consisted of children without abdominal pain in anamnesis. CCK-8 concentrations in plasma were measured with radio immunoassay technique, after plasma extraction. In study protocol we analysed CCK-8 levels in fasting state and 15, 30, 60 minutes after a standard test meal. RESULTS: In the fasting state plasma levels of CCK-8 were similar in each group and in controls. In the IBS patients CCK-8 levels were not increased after meal. In groups 1, 3 and controls postprandial levels were higher when compared to fasting state (p<0.05). Area under curve of CCK-8 plasma concentration was the lowest in group 2, but not significant compared to controls and other groups. No correlation was found between main symptoms of FD and IBS and CCK-8 concentration in plasma. CONCLUSIONS: We conclude that gut dysmotility and symptoms of functional abdominal pain in children are not concerned with alteration of plasma CCK-8 levels before and after meal.

Pancreatic exocrine secretion and plasma concentration of some gastrointestinal hormones in response to abomasal infusion of starch hydrolyzate and/or casein.

Eight Angus steers (290 +/- 8 kg), surgically prepared with pancreatic pouch-duodenal reentrant cannulas and abomasal infusion catheters were used in a replicated 4 x 4 Latin square experiment to investigate the effects of abomasal infusion of starch hydrolyzate (SH) and/or casein on pancreatic exocrine secretion and plasma concentration of hormones. Steers were fed a basal diet of alfalfa (1.2 x NEm) in 12 equal portions daily. Abomasal infusion treatments (6-L total volume infused per day) were water (control), SH [2.7 g/(kg BW x d)], casein [0.6 g/(kg BW x d)], and SH + casein. Periods were 3 d for adaptation and 8 d of full infusion. Pancreatic juice and jugular blood samples were collected over 30-min intervals for 6 h on d 11. Weight and pH of pancreatic samples were measured, and a 10% subsample was composited and frozen until analysis of total protein and pancreatic enzyme activities. The remaining sample was returned to the duodenum. Plasma was harvested and frozen until analyzed. Pancreatic juice (67 mL/h) and protein (1.8 g/h) secretion rates were not affected by nutrient infusion. There were SH x casein interactions for all pancreatic enzyme secretions (U/h; alpha-amylase, P < 0.03; trypsin, P < 0.08; and chymotrypsin, P < 0.03) and plasma insulin concentration (P < 0.10). Secretion of pancreatic enzymes was increased by SH (trypsin) and casein (alpha-amylase, trypsin, and chymotrypsin) but not when SH + casein were infused together. Glucose (P < 0.10) and cholecystokinin octapeptide concentrations (CCK-8; P < 0.05) were increased by SH, but glucagon was decreased (P < 0.10). Casein decreased (P < 0.10) plasma CCK-8 concentrations. These data indicate that positive effects of postruminal casein on enzyme secretion were inhibited by SH, emphasizing the complexity of the regulatory mechanisms involved in dietary adaptation of pancreatic exocrine secretion. Changes in hormone concentration may not relate directly to changes in enzyme secretion.

Differential bile-pancreatic secretory effects of CCK-58 and CCK-8.

In this work, we 1) synthesized rat CCK-58, 2) determined the amounts and forms of rat CCK in whole blood after stimulation of its release by casein, 3) determined the potency of CCK-8 and CCK-58 peptides to displace labeled CCK-8 from CCK(A) and CCK(B) receptors transfected into Chinese hamster ovary (CHO) cells, and 4) examined the biological actions of CCK-8 and rat CCK-58 in an anesthetized rat model. CCK-58 was the only detected endocrine form of CCK in rat blood. Synthetic rat CCK-58 was less potent than CCK-8 for displacing the label from CCK(A) and CCK(B) receptors in transfected CHO cells. However, rat CCK-58 was more potent than CCK-8 for stimulation of pancreatic protein secretion in the anesthetized rat. In addition, CCK-58 but not CCK-8 stimulated fluid secretion in this anesthetized rat model. These data suggest that regions outside the COOH terminus of rat CCK-58 influence the expression of CCK biological activity. The presence of only CCK-58 in the circulation and the fact that its biological activity differs from CCK-8 suggests that CCK-58 deserves scrutiny in other physiological models of CCK activity.

CCK-58 is the only detectable endocrine form of cholecystokinin in rat.

CCK-58 differs from CCK-8 in patterns of expression of pancreatic secretion of fluid and amylase and gallbladder contraction. These differences have physiological relevance only if CCK-58 release is stimulated by nutrients entering the intestine and if CCK-58 circulates in sizeable amounts. In this study, we report that when radiolabeled CCK-58 is added to rat blood and plasma is formed, there is extensive loss and degradation of the radioactive peptide. Therefore, a new method was developed to minimize loss and degradation of this label. This method recovered >85% of the label with no detectable degradation. Furthermore, the optimized method recovered all unlabeled exogenous cholecystokinin molecular forms in >80% yields. Blood from fasted rats and rats in which cholecystokinin release was stimulated by the trypsin inhibitor camostat contained only CCK-58 (3.5 +/- 0.5 and 17 +/- 1.5 fmol/ml, respectively). Because CCK-58 predominates in the blood, this molecular form should be used in studies on the physiology and pathophysiology of cholecystokinin.

Comparison of fatty meal and intravenous cholecystokinin infusion for gallbladder ejection fraction.

UNLABELLED: Gallbladder ejection fraction (GBEF) measured with a fatty meal (half-and-half milk) was compared with that measured with 2 equal sequential intravenous infusions of cholecystokinin (CCK-8) in a paired study of healthy subjects. METHODS: GBEF was measured by (99m)Tc-hepatic iminodiacetic acid cholescintigraphy in 13 healthy subjects. Each subject received 2 sequential doses of CCK-8 (3 ng/kg/min for 10 min) on day 1, followed by, on day 2, a 240-mL (8 oz) fatty meal (half-and-half milk) per 70 kg of body weight. RESULTS: The mean +/- SD GBEF of 53.6% +/- 20.2% with fatty meal was significantly lower than the mean of 75.8% +/- 16.3% (P < 0.01) with the first dose of CCK-8 and 71.3% +/- 17.4% (P < 0.05) with the second dose. Fatty meal GBEF varied widely, from 23.5% to 91.8%. Percentile rankings of the fatty meal GBEF were determined as the preferred methodology for reporting results. Latent and ejection periods were significantly longer with fatty meal than with either dose of CCK-8. CONCLUSION: GBEF measured with fatty meal can serve as an alternative method to intravenous injection of CCK-8 when the hormone is no longer available for clinical use. The measurement of GBEF with fatty meal requires careful attention to the details of the meal and the measurement time sequence.

Aging and panicogenic response to cholecystokinin tetrapeptide: an examination of the cholecystokinin system.

Older age is associated with diminished symptomatic and cardiovascular response to the panicogenic agent cholecystokinin tetrapeptide (CCK-4). We hypothesized that circulating concentrations of endogenous CCK-4 and/or CCK-8 are increased in later life, possibly due to decreased enzymatic degradation, and that this is associated with desensitization of CCK-B receptors. The study group consisted of 20 healthy subjects aged 18-30 years and 20 healthy subjects aged 65-85 years. The two groups were compared on fasting basal plasma concentrations of CCK-4, sulfated CCK-8 (CCK-8s) and nonsulfated CCK-8 (CCK-8 ns), and on binding capacity of lymphocyte CCK-B receptors. Under single-blind (to subject) conditions, subjects were then administered an intravenous bolus of placebo, followed 50 min later by an intravenous bolus of 50 micro g of CCK-4. Plasma concentrations of total CCK (CCK(T)) were measured 2 min before and 2, 5, 10, and 15 min after each injection. Compared with younger subjects, older subjects had a significantly higher basal plasma concentration of CCK-8s and significantly diminished binding capacity of CCK-B receptors. Following injection of placebo, plasma CCK(T) concentrations did not significantly change from baseline in either age group, but the elderly had significantly higher concentrations than the young at 2, 5, and 10 min. Following injection of CCK-4, the plasma concentration of CCK(T) was highest at 2 min and declined after that. The elderly had significantly higher CCK(T) concentrations (ie. a slower decline in CCK(T)) than the young at 5, 10, and 15 min. These findings are consistent with our hypothesis and suggest that age-related changes in the CCK system could contribute to the diminished panicogenic response to exogenous CCK-4 in older persons.