Cholecystokinin Concentrations Research Articles

Effect of Liangruntongluo Recipe and its Modified Formula on Gastrointestinal MOT、 CCK、SS of Rats with Diabetes

Objective To study the mechanism of Liangruntongluo Recipe (Chinese medicines with functions of cooling, nourishing and dredging collaterals) and its modified formula in improving gastrointestinal function of diabete smellitus (DM) rats. Methods Male Wistar rats were used. Streptozotocin (STZ) was injected to rats to produce diabetic rat models. No Hypoglycemic drugs were administered to these rats to reduce blood glucose. After 18 weeks, warm water, Liangruntongino Recipe, Chinese medicines with function of nourishing, Chinese medicines with functions of cooling, and Cisapride were administered to the model rats. Detect the contents of plasma motilin (MOT), cholecystokinin (CCK), and somatostatin (SS) after 6 weeks. Results By affecting the secretion of gut hormone and having wide range of target, Liangrantongluo Recipe could regulate the disorder of gut hormone. The function of Liangruntongluo Recipe was better than its modified formula and cisapride.Conclusion Liangruntongluo Recipe can improve gastrointestinal dysfunction of DM rats. Key words: Liangruntongluo Recipe; Diabetic gastrointestinal dysfunction; Motilin (MOT): Cholecystokinin(CCK); Somatostatin (SS)

Comparative effects of intraduodenal infusions of lauric and oleic acids on antropyloroduodenal motility, plasma cholecystokinin and peptide YY, appetite, and energy intake in healthy men

BackgroundThe regulation of gastrointestinal function and energy intake by fatty acids depends on their chain length. Animal studies suggest that lauric acid (C12) may have more potent suppressive effects on energy intake than does oleic acid (C18). ObjectiveWe compared the effects of equicaloric loads of C12 and C18 on antropyloroduodenal (APD) motility, plasma concentrations of cholecystokinin (CCK) and peptide YY (PYY), appetite, and energy intake. DesignThirteen healthy men (aged 20–46 y) were studied on 3 occasions in double-blind, randomized fashion. APD pressure waves, plasma hormones, and appetite perceptions were measured during 60-min intraduodenal infusions of 1) C12, 2) C18, or 3) 0.9% saline as control (rate: 4 mL/min; energy load for C12 and C18: 0.4 kcal/min); between 60 and 90 min, the subjects consumed a meal. Energy intake at a buffet meal was quantified. ResultsC12 and C18 both reduced antral (P < 0.001) and duodenal (P < 0.01) pressure waves and stimulated isolated pyloric pressure waves (P < 0.01) and plasma CCK (P < 0.001), with no differences between them. Although C12 and C18 both increased basal pyloric pressure (P < 0.05), C12 had a greater effect than did C18 (P < 0.01). In contrast, although both C12 and C18 increased plasma PYY (P < 0.001), C18 had a greater effect than C12. C12, but not C18, suppressed energy intake (P < 0.05). ConclusionsAt the load administered, C12, but not C18, suppressed energy intake, and C12 was a more potent stimulant of basal pyloric pressure. These discrepant effects are not apparently accounted for by changes in CCK or PYY secretion.

The impact of delaying enteral feeding on gastric emptying, plasma cholecystokinin, and peptide YY concentrations in critically ill patients*

Enteral nutrient (EN) deprivation slows gastric emptying (GE) and increases plasma cholecystokinin (CCK) concentrations in healthy humans and may potentially contribute to the delayed GE in the critically ill. This study examined the impact of delayed feeding on GE, plasma CCK, and peptide YY (PYY) concentrations in the critically ill. Randomized controlled trial. Mixed medical and surgical intensive care unit (ICU). Twenty-eight critically ill patients were randomized to receive EN either within 24 hrs of admission ("early feeding": 54.9 +/- 3.3 yrs; Acute Physiology and Chronic Health Evaluation (APACHE) II = 23.0 +/- 1.8) or on day 4 of admission after GE assessment ("delayed feeding": 56.1 +/- 4.2 yrs, APACHE II = 21.7 +/- 1.8). GE of 100 ml of Ensure was measured using scintigraphy on day 4 of admission. Blood was sampled for measurement of plasma CCK, PYY, and glucose concentrations. Demographics, APACHE II score, use of inotrope and morphine sedation were similar between the groups. The mean administered/prescribed caloric ratio in the "early feeding" group was 72 +/- 4%. There were no differences in the retention of meal, intragastric meal distribution, proportion of patients with delayed GE (9/14 vs. 9/14), and plasma CCK and PYY concentrations during fasting and postprandially between the two groups. There was no relationship between the number of calories received and percentage of meal retention at 240 min (p > .05). However, delayed feeding was associated with longer duration of mechanical ventilations (13.7 +/- 1.9 vs. 9.2 +/- .9 days, p = .049) and length of stay in ICU (15.9 +/- 1.9 vs. 11.3 +/- 0.8 days, p = .048), but no difference in mortality. In critical illness, delayed enteral feeding appears to have little impact on either GE or the enterogastric feedback hormones. However, the association between delayed feeding and increased duration of ventilation and length of stay in the ICU supports the current recommendation that enteral nutrition should be commenced early.

Effects of Yanggan Lidan Granule on rate of gallstone formation and content of plasma cholecystokinin in guinea pigs with induced cholesterol gallstones

To explore the effects of Yanggan Lidan Granule (YGLDG), a compound traditional Chinese herbal medicine for nourishing liver and improving choleresis, on the rate of gallstone formation and content of plasma cholecystokinin in guinea pigs with induced cholesterol gallstones. Eighty guinea pigs were randomly divided into 4 groups, which were normal control group, untreated group, YGLDG-treated group and ursodeoxycholic acid (UDCA)-treated group (n=20). Except the normal control group, gallstones were induced by high-cholesterol diet in the guinea pigs. YGLDG (1.81 g/kg daily) and UDCA (30.12 mg/kg daily) were given orally to guinea pigs in the corresponding group respectively for seven weeks; however, the guinea pigs of normal control group and untreated group were administered with normal saline. The physical signs of the guinea pigs and the rates of gallstone formation were examined, and the content of cholecystokinin (CCK) in the plasma was detected by radio-immunoassay. YGLDG could obviously improve the ethological signs of the guinea pigs. Gallstone formation rate of the untreated group (82.35%) was significantly increased as compared with that of the normal control group (5.26%) (P<0.01), while the gallstone formation rates of the YGLDG-treated group (27.28%) and UDCA-treated group (38.89%) were lower than that of the untreated group (P<0.05). The content of CCK in plasma of the untreated group was significantly lower than that of the normal control group (P<0.01), while CCK content of the YGLDG-treated group and UDCA-treated group was lower than that of the normal control group, but both of them were significantly higher than that of the untreated group (P<0.01). The difference of CCK levels between YGLDG-treated group and UDCA-treated group had no statistical significance (P>0.05). YGLDG can significantly decrease the rate of gallstone formation in guinea pigs. It may be related to elevating the content of CCK in the plasma.

Dietary Unsaturated Fatty Acids Increase Plasma Glucagon-Like Peptide-1 and Cholecystokinin and May Decrease Premeal Ghrelin in Lactating Dairy Cows

Previous reports have indicated that dietary unsaturated fat can decrease energy intake of lactating dairy cattle. However, the mechanism for this response is unclear. To evaluate the potential role of gut peptides, periprandial concentrations of cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), and ghrelin were measured. From a replicated 4×4 Latin square experiment, 4 cows from a single square were selected for analysis of responses to 3 treatments: a control diet (5.5% total fatty acids, 65% unsaturated), a diet with added saturated fat (SAT, 8.3% fatty acids, 47% unsaturated), and a diet with added unsaturated fat (UNS, 7.8% fatty acids, 63% unsaturated). The SAT treatment increased duodenal flow of saturated fatty acids compared with UNS and control and, despite the fact that ruminal biohydrogenation altered fatty acid profiles of digesta, UNS increased duodenal flow of unsaturated fatty acids compared with SAT and control. Blood samples were collected at 8-min intervals through the first 2 meals of the day and analyzed by commercial radioimmunoassays. The UNS treatment increased plasma CCK concentration relative to SAT and control, and increased plasma GLP-1 concentration compared with control. Furthermore, fat treatments tended to suppress the prandial ghrelin surge that was evident for control. Suppression of feed intake by unsaturated fats is likely mediated in part by increased secretion of CCK and GLP-1, and dietary fat may also inhibit ghrelin release before conditioned meals.

Protein kinase C in the pancreatic acinar cell

Pathological activation of selective signaling molecules within the pancreatic acinar cell mediates the development of acute pancreatitis. Some of the key early acinar cell events include activation of proteases, inhibition of apical secretion, and elaboration of inflammatory mediators. Previous studies have shown that supraphysiological concentrations of cholecystokinin (CCK) that can cause pancreatitis in vivo, also initiate these pathological responses in dispersed groups of acinar cells (acini). Protein kinase C (PKC) regulates many cellular events and a role for this family of signaling molecules has been described in some of the pathological responses of pancreatitis. Notably, ethanol can activate specific PKC isoforms and sensitize the acinar cells to the pathological effects of CCK. Our preliminary studies in isolated pancreatic acini and a cell-free reconstitution system suggest that PKC can mediate protease activation in the acinar cell. These findings may be relevant to the pathogenesis of pancreatitis from alcohol and other etiologies.

Esomeprazole reduces gastroesophageal reflux after beer consumption in healthy volunteers

Objective. Patients with gastroesophageal reflux disease (GERD) are advised to avoid alcoholic beverages since alcohol consumption induces gastroesophageal reflux in healthy volunteers and increases it in patients with GERD. Proton-pump inhibitors (PPIs) are frequently administered for reflux symptoms but their effect on gastroesophageal reflux after alcohol consumption has not yet been fully studied. The aim of the present study was therefore to investigate the effect of esomeprazole, an S-enantiomer of omeprazole, on gastroesophageal reflux after beer consumption. Material and methods. In this placebo-controlled, double-blind, crossover study, 16 healthy male volunteers received 20 mg esomeprazole daily for one week. On day 7, in an acute experiment, the subjects then consumed 500 ml beer within 5 min. Subsequently, gastroesophageal reflux was monitored by pH-metry over a period of 3 h. In addition, gastric emptying was measured by ultrasonography and blood concentrations of ethanol, cholecystokinin and gastrin were determined. Results. Gastroesophageal reflux was significantly (p=0.001) reduced by 93% after treatment with esomeprazole (0.2%, median percentage of time pH<4) as compared to placebo (2.6%), but gastric emptying, blood ethanol and cholecystokinin concentrations were not significantly different after esomeprazole treatment. Plasma gastrin levels were significantly (p=0.0003) higher after esomeprazole (98.6±19.7 pg/ml) than after placebo (22.7±3.8 pg/ml) before beer consumption. However, there was no difference in the increase in plasma gastrin after beer consumption between the esomeprazole treatment and placebo. Conclusions. Esomeprazole significantly reduces gastroesophageal reflux after beer consumption in healthy volunteers. Gastric emptying of beer is not prolonged after treatment with esomeprazole, although compared with placebo, this PPI induced significantly higher plasma gastrin concentrations. Moderate alcohol consumption does not worsen gastroesophageal reflux when a PPI is administered.

Plasma concentrations of glucagon-like peptide-1 and cholecystokinin in sheep are altered by the amount of dry matter intake and the addition of fat to the diet

Dry matter intake (DMI) regulation is important in ruminants as DMI is a major determinant of milk and meat production. It is known that the gut peptides glucagon-like peptide-17, 36 amide (GLP-1) and cholecystokinin-8 (CCK) can reduce DMI in nonruminants (Walsh, 1994). In ruminants, there is little information on the function or effects of diet on plasma concentrations of these peptides. Previous studies have shown that supplemental dietary fat (Relling and Reynolds, 2007b) increases plasma concentrations of GLP-1 and CCK and decreases DMI. In contrast, increased metabolizable energy intake (MEI) in early lactation also increases GLP-1 and CCK concentration in dairy cows (Relling and Reynolds, 2007a). Therefore, our objective was to determine if plasma concentrations of GLP-1 and CCK are affected by supplemental fat, and if the response differs for ad libitum versus restricted DMI.

Lack of Relationship between Blood Glucose-lowering Activity of Colestimide and Serum Cholecystokinin (CCK) Concentrations in Patients with Type 2 Diabetes

Colestimide has been reported to lower blood glucose levels in patients with type 2 diabetes and hypercholesterolemia. We investigated the mechanism of the hypoglycemic activity of colestimide by examining changes in serum cholecystokinin (CCK) and insulin concentrations before and after its 2-week oral administration. A total of seven type 2 diabetes inpatients with hypercholesterolemia received colestimide after their blood glucose levels had stabilized. We daily measured plasma glucose levels and serum lipid concentrations, calculated Body Mass Index (BMI), and determined whole-day changes in serum immunoreactive insulin (IRI) and CCK concentrations in all study subjects. We daily measured plasma glucose levels, as well as serum IRI and CCK concentrations at 10 time points for measurement. Plasma glucose levels, as well as serum IRI and CCK concentrations before and after the 2-week oral administration of colestimide were compared. The means of total cholesterol levels and BMI decreased significantly after administration. At time points for measurement (10 : 00 and 12 : 00), plasma glucose levels decreased significantly after administration (P=0.026 and P=0.009, respectively). Diurnal changes in serum IRI and CCK concentrations were not observed after administration, except for the IRI concentration at 20: 00. The effect of colestimide on CCK may not explain the mechanism of its blood glucose-lowering activity in patients with type 2 diabetes and hypercholesterolemia.

Visualizing formation and dynamics of vacuoles in living cells using contrasting dextran-bound indicator: endocytic and nonendocytic vacuoles

Here we describe a technique that allows us to visualize in real time the formation and dynamics (fusion, changes of shape, and translocation) of vacuoles in living cells. The technique involves infusion of a dextran-bound fluorescent probe into the cytosol of the cell via a patch pipette, using the whole-cell patch-clamp configuration. Experiments were conducted on pancreatic acinar cells stimulated with supramaximal concentrations of cholecystokinin (CCK). The vacuoles, forming in the cytoplasm of the cell, were revealed as dark imprints on a bright fluorescence background, produced by the probe and visualized by confocal microscopy. A combination of two dextran-bound probes, one infused into the cytosol and the second added to the extracellular solution, was used to identify endocytic and nonendocytic vacuoles. The cytosolic dextran-bound probe was also used together with a Golgi indicator to illustrate the possibility of combining the probes and identifying the localization of vacuoles with respect to other cellular organelles in pancreatic acinar cells. Combinations of cytosolic dextran-bound probes with endoplasmic reticulum (ER) or mitochondrial probes were also used to simultaneously visualize vacuoles and corresponding organelles. We expect that the new technique will also be applicable and useful for studies of vacuole dynamics in other cell types.

A Carbohydrate-Restricted Diet Alters Gut Peptides and Adiposity Signals in Men and Women with Metabolic Syndrome ,

Carbohydrate-restricted diets have been shown to enhance satiation- and other homeostatic-signaling pathways controlling food intake and energy balance, which may serve to reduce the incidence of obesity and metabolic syndrome. This study was designed as a correlational, observational investigation of the effects of a carbohydrate-restricted diet on weight loss and body fat reduction and associated changes in circulating leptin, insulin, ghrelin, and cholecystokinin (CCK) concentrations in overweight/obese patients (4 men and 16 women) with metabolic syndrome. Subjects received clinical instruction on the initiation and maintenance of the commercial South Beach Diet, consisting of 2 phases: Phase I (initial 2 wk of the study) and Phase II (remaining 10 wk). Participants showed a decrease (P < 0.05) in body weight (93.5 α 3.6 kg vs. 88.3 α 3.4 kg), BMI (33.9 α 1.3 kg/m2 vs. 32.0 α 1.3 kg/m2), waist circumference (112.8 α 2.8 cm vs. 107.7 α 3.0 cm), and total percent body fat (40.2 α 1.5% vs. 39.2 α 1.5%) by study completion. Plasma fasting insulin and leptin concentrations decreased significantly from baseline concentrations (139.1 α 12.2 pmol/L and 44.1 α 4.5 μg/L, respectively) by the end of Phase I (98.6 α 2.6 pmol/L and 33.3 α 4.1 μg/L, respectively). Plasma fasting ghrelin concentrations significantly increased from baseline (836.7 α 66.7 ng/L) by Phase II (939.9 α 56.8 ng/L). The postprandial increase in plasma CCK concentrations (difference in plasma CCK concentrations from fasting to postprandial) after Phase I (2.4 α 0.3 pmol/L) and Phase II (2.5 α 0.4 pmol/L) was significantly greater than the postprandial increase at baseline (1.1 α 0.5 pmol/L). Collectively, these results suggest that in patients with metabolic syndrome, improved adiposity signaling and increased postprandial CCK concentrations may act together as a possible compensatory control mechanism to maintain low intakes and facilitate weight loss, despite an increase in fasting ghrelin concentrations and subjective measures of hunger.

Free Fatty Acids Have More Potent Effects on Gastric Emptying, Gut Hormones, and Appetite Than Triacylglycerides

The effects of fat on gastric emptying (GE), gut hormones, and energy intake are dependent on digestion to free fatty acids (FFAs). In animals, small intestinal oleic acid inhibits energy intake more potently than the triacylglyceride (TG) triolein, but there is limited information about the comparative effects of FFA and TG in human beings. We compared the effects of FFA and TG on GE, gut hormone secretion, appetite, and energy intake in healthy males. Nine men (age, 23 +/- 2 y; body mass index, 22 +/- 1 kg/m(2)) were studied on 3 occasions to evaluate the effects of (1) 40 g oleic acid (FFA, 1830 kJ), (2) 40 g macadamia oil (TG, 1856 kJ; both 600-mL oil-in-water emulsions stabilized with 4% milk protein and labeled with 15 MBq (123)I), or (3) 600 mL 4% milk protein (control, 352 kJ), administered intragastrically, on GE, plasma cholecystokinin (CCK) and peptide-YY (PYY) levels, appetite perceptions, and subsequent energy intake. GE of FFA was much slower than that of TG (P < .05), with greater retention of FFA, than TG, in the proximal stomach (P < .001). Hunger was less (P < .05), and fullness was greater (P < .05), after FFA when compared with control and TG. Increases in plasma CCK and PYY levels were greater after FFA than TG or control (P < .05). Energy intake tended to be less after FFA compared with TG (control, 4754 +/- 610 kJ; TG, 5463 +/- 662 kJ; FFA, 4199 +/- 410 kJ). FFAs empty from the stomach more slowly, but stimulate CCK and PYY and suppress appetite more potently than TG in healthy human beings.

Effect of intravenous infusion of proglumide on ruminal motility in conscious sheep (Ovis aries)

The effects of intravenous infusion of proglumide on regular ruminal contractions were examined in conscious sheep using doses that inhibit pancreatic exocrine secretion. After a control period of 20 min, proglumide was infused intravenously for 40 min at a dose of 15, 30 or 60 micromol/kg per min and venous blood was collected. The intravenous infusion of proglumide significantly increased the frequency of ruminal contractions at 15 micromol/kg per min without altering the amplitude, while it significantly decreased the frequency and amplitude of ruminal contractions at 30 and 60 micromol/kg per min in a dose-dependent manner. Proglumide did not increase contractile activity of the omasum, abomasum and duodenum or the plasma concentration of immunoreactive cholecystokinin (CCK). Application of proglumide at 1-30 mmol/L inhibited bethanechol-induced contraction in both longitudinal and circular muscle strips of the dorsal sac of the rumen. These results suggest that proglumide at a low dose acts indirectly on the rumen as a CCK receptor antagonist to increase the frequency of contractions, whereas at higher doses it inhibits cholinergic-induced contraction of the ruminal muscles or acts as an agonist to inhibit contractions in sheep. Hence, proglumide at high doses seems unsuitable for research or therapeutic use as a CCK receptor blockade in sheep.

Feed intolerance in critical illness is associated with increased basal and nutrient-stimulated plasma cholecystokinin concentrations*

Delayed gastric emptying and intolerance to gastric feeding occur frequently in the critically ill. In these patients, gastric motor responses to nutrients are disturbed. Cholecystokinin (CCK) slows gastric emptying. The aim of this study was to determine plasma CCK concentrations during fasting and in response to small-intestine nutrient infusion in critically ill patients. Randomized, controlled trial. Level 3, mixed medical and surgical intensive care unit. A total of 31 mechanically ventilated, critically ill patients (23 men, 51 +/- 3 yrs) and 28 healthy subjects (21 men, 43 +/- 2 yrs). Subjects received two 60-min duodenal infusions of Ensure (complete balanced nutrition), at 1 and 2 kcal/min, in a randomized, single-blind fashion. The nutrient infusions were separated by a 2-hr "washout" period. Blood samples for measurement of plasma CCK concentrations were obtained immediately before and every 20 mins during nutrient infusion. Baseline and nutrient-stimulated plasma CCK concentrations were higher in critically ill patients compared with healthy subjects (p < .001). The magnitude of the rise in plasma CCK in response to nutrients was also greater in the critically ill (p < .01). Of the 23 patients who received enteral nutrition before the study, nine were intolerant of gastric feeding. In these patients, both the baseline plasma CCK concentration and the magnitude of CCK increase during nutrient infusions were greater than in patients with feed tolerance (p < .002). Impaired renal function was associated with an increased baseline CCK concentration but had no effect on the CCK response to nutrients. Both fasting and nutrient-stimulated plasma CCK concentrations are increased in critically ill patients, particularly in those with feed intolerance. This may provide a humoral mechanism for delayed gastric emptying seen in critical illness.

Lack of Trophic Pancreatic Effects in Humans With Long-term Administration of Ximelagatran

Negative feedback regulation of pancreatic proteases controls pancreatic secretion in most species and pancreatic growth in rodents. Its mechanism involves the inhibition of intraluminal proteases, resulting in sustained elevation of plasma cholecystokinin (CCK) concentrations, producing a chronic trophic stimulus to the pancreas that leads to the formation of pancreatic nodules and adenomas. Ximelagatran, whose active form, melagatran, inhibits both thrombin and the serine protease trypsin, is under clinical development as an oral anticoagulant. Recent data indicate species differences in the expression of CCK receptor subtypes in the pancreas. CCK1 receptors are abundant in rat pancreas but are either absent or present at very low levels in human pancreas. As part of the clinical studies, we examined whether long-term ximelagatran administration causes CCK release and exerts possible trophic effects on the pancreas in humans. One hundred thirty patients requiring anticoagulation treatment for atrial fibrillation randomly received, in a double-blind fashion, either 36 mg oral ximelagatran twice daily or warfarin dose adjusted to an international normalized ratio of 2.0 to 3.0. Before enrollment and after 12 months of treatment, computed tomography scans of the pancreas were performed, and pancreas volumes were quantified using the summation-of-areas technique. Three months after the initiation of drug treatment, plasma CCK concentrations were measured by radioimmunoassay 120 minutes after the patients drank 240 mL of a mixed liquid meal (Ensure). After 3 months of treatment, plasma CCK concentrations did not differ between the ximelagatran and warfarin groups, 15 +/- 18 and 11 +/- 17 pmol/L (X +/- SD; P = 0.22), respectively. The initial average pancreas volumes were 82 +/- 31 and 88 +/- 28 mL in the ximelagatran and warfarin groups, respectively, and decreased to 70 +/- 25 and 75 +/- 28 mL, respectively, after 12 months of treatment. Although the decrease in pancreas volume with time was significant in each group (P = 0.0001), the magnitude of the volume reduction was similar in the 2 groups. In contrast to rats, in which long-term oral administration of ximelagatran stimulates pancreatic growth and adenoma formation, in humans, ximelagatran does not increase plasma CCK concentrations and has no demonstrable trophic effect on the human pancreas.

Elevation of plasma cholecystokinin concentration following a meal is increased by gonadectomy in male cats*

An overweight or obese body condition commonly develops after gonadectomy (GX) in domestic cats. The cause appears to be a rapid, quantal (approximately 12%), increase in food intake that is sustained and probably mediated by withdrawal of gonadal hormone. Recently, an interaction of gonadal hormone and cholecystokinin (CCK) effectiveness has been suggested. A reduction in the satiating potency of intestinal CCK was presently hypothesized to contribute to the disturbance of food intake control caused by GX in domestic cats. Pre- and post-prandial intestinal CCK secretion as indicated by plasma CCK concentrations were determined in 16 adult male cats (5.1 +/- 0.1 kg) 8 weeks before and 57 weeks after eight of the cats were gonadectomized. During ad libitum intake of a commercial dry, expanded diet, body weight increased from 22% to 28% in gonadectomized cats and was unchanged in intact cats. Baseline CCK concentrations were not different between gonadectomized and intact cats. Amounts of diet ingested during CCK determinations were 15-19% of daily metabolizable energy requirement and were not different between gonadectomized and intact cats. The post-prandial area under the curve (AUC; 0-400 min) CCK concentration increased linearly with meal size (p < 0.01) and was not correlated with body weight. Area under the curve CCK concentration, when normalized for meal size, was 34% greater (p < 0.01) in gonadectomized cats than that in intact cats. The findings indicate GX increases meal-induced intestinal CCK secretion and therefore, do not support the study hypothesis. The findings indicate GX may slow digestion and absorption and attenuate inhibition of food intake by CCK.

Sex and Cognitive Dietary Restraint Influence Cholecystokinin Release and Satiety in Response to Preloads Varying in Fatty Acid Composition and Content

The aim of the study was to evaluate the effect of preloads differing in fatty acid composition, content, and delivery form on acute behavioral, subjective, and biological outcomes of satiety. Four energy- and volume-matched preloads were tested in normal weight men and women (n = 12 and 13, respectively), using a random, crossover design. Preloads were semisolid shakes differing in fat source [walnut or safflower (SAFF)], delivery [ground walnuts (WNT) or walnut oil (WOL)] or content [39% fat energy (SAFF, WNT, WOL) or 4% low-fat control (LFC)]. Blood was collected and subjective satiety assessed at 0 (fasting), 15, 30, and 45 min after preload consumption. Lunch (test meal) was provided thereafter. Energy intake at lunch was not affected by preload; however, subjects selected more carbohydrate, fiber-rich foods at the test meal lunch after walnut preloads than after LFC or SAFF preloads. Compared with the LFC preload, appetite satisfaction was significantly greater after SAFF and WNT, but not after WOL. Women were hungrier after SAFF than after WOL, whereas men were less hungry after SAFF and LFC than after WOL or WNT. Plasma cholecystokinin (CCK) concentrations reflected preload fat content and availability, particularly among men; CCK was higher after WOL and SAFF preloads than after LFC or WNT preloads. Plasma insulin was higher after LFC and SAFF preloads, corresponding to hunger suppression in men. Dietary restraint was associated with a blunted CCK response to preloads, whereas insulin was not affected by restraint. The results indicate that test meal energy intake after preloads containing approximately 40% walnut or safflower fat or 4% fat did not differ; however, walnut consumption may promote food patterns consistent with consuming diets higher in fiber.

Role of NAADP and cADPR in the Induction and Maintenance of Agonist-Evoked Ca2+ Spiking in Mouse Pancreatic Acinar Cells

Nicotinic acid adenine dinucleotide phosphate (NAADP) and cyclic adenosine diphosphate ribose (cADPR) were first demonstrated to mobilize Ca2+ in sea urchin eggs. In the absence of direct measurements of these messengers, pharmacological studies alone have implicated these molecules as intracellular second messengers for specific cell surface receptor agonists. We now report that in mouse pancreatic acinar cells, cholecystokinin, but not acetylcholine, evokes rapid and transient increases in NAADP levels in a concentration-dependent manner. In contrast, both cholecystokinin and acetylcholine-mediated production of cADPR followed a very different time course. The rapid and transient production of NAADP evoked by cholecystokinin precedes the onset of the Ca2+ signal and is consistent with a role for NAADP in the initiation of the Ca2+ response. Continued agonist-evoked Ca2+ spiking is maintained by prolonged elevations of cADPR levels through sensitization of Ca2+ -induced Ca2+ -release channels. This study represents the first direct comparison of NAADP and cADPR measurements, and the profound differences observed in their time courses provide evidence in support of distinct roles of these Ca2+ -mobilizing messengers in shaping specific Ca2+ signals during agonist stimulation.

Vacuolar ATPase Regulates Zymogen Activation in Pancreatic Acini

Supramaximal concentrations of cholecystokinin or its analogue caerulein have been shown to stimulate the proteolytic activation of zymogens within the pancreatic acinar cell and initiate acute pancreatitis. Previous studies suggest that a low pH compartment might be required for activation. To test this hypothesis, the effects of agents that modulate intracellular pH on caerulein-induced trypsin and chymotrypsin activation were studied. Pretreatment of pancreatic acini with the proto-ionophore monensin (10 microM) and the weak base chloroquine (40 microM) inhibited activation. Pre-incubation with the vacuolar ATPase (V-ATPase) inhibitors bafilomycin A(1) and concanamycin A also decreased activation in a concentration-dependent manner with 50% inhibition at approximately 50 and 25 nM, respectively. Caerulein stimulation caused a time- and concentration-dependent translocation of soluble V-ATPase V(1) subunits to a membrane fraction, a marker of V-ATPase activation. Carbachol also stimulated translocation at supramaximal concentrations. Elevation of cytosolic Ca(2+) by thapsigargin was sufficient to induce translocation. Thus, stimulation of V-ATPase activity appears to be required for agonist-induced zymogen activation in the pancreatic acinar cell.

Entero-insular axis in children with anorexia nervosa

Entero-insular axis plays an important role in generating satiety signal. Thus disturbances in this axis may influence the course of anorexia nervosa. The aim of the study was analysis of the function of the hormonal part of the entero-insular axis in girls with anorexia nervosa. Thirteen girls with anorexia nervosa and in 10 healthy girls were studied. Each girl was subjected to oral glucose tolerance test and standard meal test. Blood was collected before stimulation and within 15, 30, 60, and 120 min thereafter. The concentrations of all peptides were determined by radioimmunoassay commercial kits. Fasted and postprandial levels of these peptides as well as integrated outputs were measured. Fasting insulin concentration was significantly higher in the group of girls with anorexia nervosa than in the control group (p<0.03). What more in girls with anorexia the integrated output of insulin was significantly lower in oral glucose tolerance test than after the meal (p<0.001). Also the integrated output of glucagon in both tests was higher in the group of girls with anorexia than in the control group. The mean output of pancreatic polypeptide and cholecystokinin in anorexia group was significantly higher (p<0.001 in both cases) than that in the control group but only after the test meal. The integrated outputs of gastric inhibitory peptide in both tests were significantly higher in anorectic girls than those in the control group (oral glucose tolerance test, p<0.02; meal test, p<0.001), However, mean values of the integrated output of glucagon-like peptide 1 in both tests were significantly higher in the control group than in the girls with anorexia (p<0.001 in each case). Highly significant correlation was found between glucose concentration and the concentrations of insulin, cholecystokinin, and gastric inhibitory peptide in both tests and for the both groups. In the anorectic girls, significant correlation between insulin concentration and the concentration of gastric inhibitory peptide was found after both stimulation tests and between insulin and cholecystokinin after oral glucose only. the disturbed secretion of the hormones of entero-insular axis after the meal in anorectic girls may have negative influence on the course of anorexia nervosa. This disease has no effect on the incretin function of cholecystokinin, gastric inhibitory peptide and glucagon-like peptide 1.