CCK Concentrations Research Articles

Effect of intraperitoneal and intravenous administration of cholecystokinin-8 and apolipoprotein AIV on intestinal lymphatic CCK-8 and apo AIV concentration

Effect of intraperitoneal and intravenous administration of cholecystokinin-8 and apolipoprotein AIV on intestinal lymphatic CCK-8 and apo AIV concentration

Effect of age and frailty on ghrelin and cholecystokinin responses to a meal test

Background:Ghrelin and cholecystokinin (CCK) are among the peripheral signals that regulate hunger and satiety. Objective:The objective was to assess whether ghrelin and CCK responses to a standard nutritional load are related to age and frailty. Design:Ghrelin, CCK, insulin, glucose, and 4-h visual analog hunger scale curves after a standard nutritional load test (380 kcal) were described and compared between 3 groups: old (>75 y) and frail persons (group A), old (>75 y) but nonfrail persons (group B), and young (25–65 y) adults (group C). Results:Frail persons showed no postprandial ghrelin suppression, and old subjects, frail and nonfrail, showed no significant postprandial ghrelin recovery compared with young adults. Frailty was also associated with lower fasting ghrelin concentrations. No differences in fasting CCK were observed between young and old persons; however, postprandial CCK concentrations were enhanced in young persons, whereas no frailty effect on the CCK curve was observed in the old subjects. No correlations between mean ghrelin and hunger values over time were found, but strong negative correlations were shown between CCK and hunger (group A: rs = −0.88, P = 0.009; group B: rs = −0.86, P = 0.014; group C: rs = −0.71, P = 0.071) and insulin and hunger (group A: rs = −0.901, P = 0.006; group B: rs = −0.964, P < 0.001; group C: rs = −0.929, P = 0.003). Conclusions:Advanced age determines a poorer ghrelin postprandial recuperation phase, a reduced CCK postprandial response, and an exaggerated postprandial insulin release. A loss of ghrelin prandial rhythm is present in old frail persons. The impaired response of these hunger regulatory hormones with age might contribute to the mechanisms of anorexia associated with aging.

Food intake, appetite, gut hormones, and resting energy expenditure in resistance trained vs. sedentary older adults

ObjectiveTo assess the effects of chronic resistance training (RT) on food intake, appetite, fasting gut hormones, and energy expenditure (EE) in 16 RT and 35 sedentary (Sed) older persons (62‐84 y).MethodsFree‐living energy intake and appetite sensations (hunger, fullness and desire to eat) were assessed on 3 days (2 weekdays, 1 weekend day) and fasting‐state resting EE, plasma glucose and gut hormones (Cholecystokinin, CCK; glucagon‐like peptide‐1, GLP‐1; insulin; ghrelin) were measured.ResultsMaximum strength was higher for RT (8.3 ± 0.3) vs. Sed [6.9 ± 0.2 kg/kg fat free mass (*, p&lt;0.05); mean ± SE]. RT did not affect total energy (RT 2079 ± 79 vs. Sed 1995 ± 66 kcal/d), protein, carbohydrate and fat intakes. Hunger and desire to eat area under the curve (AUC) values were not different between groups. Fullness AUC was lower in RT (0.4 ± 0.2) vs. Sed (0.9 ± 0.3* AU·720 min). EE was not different between groups, and respiratory exchange ratio tended to be lower in the RT (0.87 ± 0.00) vs. Sed (0.89 ± 0.01, p=0.06). CCK was higher in RT (0.71 ± 0.38) vs. Sed (0.51 ± 0.05* ng/mL), and GLP‐1 was lower in RT (0.31 ± 0.32) vs. Sed (1.45 ± 0.19* ng/mL). RT did not affect glucose, insulin, and ghrelin.ConclusionsRT alters fasting concentrations of CCK and GLP‐1. However, despite the isolated differences in appetitive sensations and gut hormones, RT did not influence EI.Grant Funding SourceNIH R01 AG021911, Purdue Bilsland Fellowship

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.

The versatility of the vagus

The gut is one of several organs contributing to the peripheral signalling network that controls food intake. Afferent neurons of the vagus nerve provide an important pathway for gut signals that act by triggering ascending pathways from the brain stem to hypothalamus. Recent work indicates the existence of mechanisms operating at the level of vagal afferent neurons to modulate the effect of gastrointestinal satiety signals. Thus, the well known satiety hormone cholecystokinin (CCK) not only stimulates the discharge of these neurons but also controls their expression of both G-protein coupled receptors and peptide neurotransmitters known to influence food intake. When plasma CCK concentrations are low e.g. in fasting, the expression by vagal afferent neurons of cannabinoid (CB)-1 and melanin concentrating hormone (MCH)-1 receptors is increased. Release of CCK by feeding leads to a rapid down-regulation of expression of both receptors and to increased expression of Y2 receptors. In fasting, there is also increased expression in these neurons of the appetite-stimulating neuropeptide transmitter MCH, and depressed expression of the satiety-peptide cocaine and amphetamine regulated transcript (CARTp); endogenous CCK decreases MCH expression and stimulates CART expression. The gastric orexigenic hormone ghrelin blocks these actions of CCK at least in part by excluding phosphoCREB from the nucleus. The data suggest that CCK acts as a gatekeeper to determine the capacity of other neuroendocrine signals to act via vagal afferent neurons to influence food intake.

Low ambient temperature lowers cholecystokinin and leptin plasma concentrations in adult men

Background: It is known that the low ambient temperature causes a considerable increase of appetite. The mechanisms underlying the changes of the amounts of the ingested food in relation to the environmental temperature has not been elucidated. The aim of this study was to investigate the effect of the short exposure to low ambient temperature on the plasma concentration of leptin and cholecystokinin. Methods: Sixteen healthy men, mean age 24.6 ± 3.5 years, BMI 22.3 ± 2.3 kg/m 2 , participated in the study. The concen- trations of plasma CCK and leptin were determined twice - before and after the 30 min. exposure to + 4 °C by using RIA kits. Results: The mean value of CCK concentration before the exposure to low ambient temperature was 1.1 pmol/l, and after the exposure 0.6 pmol/l (p<0.0005 in the paired t-test). The mean values of leptin before exposure (4.7 ± 1.54 μg/l) were also significantly lower than after the exposure (6.4 ± 1.7 μg/l; p<0.0005 in the paired t-test). However no significant cor- relation was found between CCK and leptin concentrations, both before and after exposure to low temperature. Conclusions: It has been known that a fall in the concentration of CCK elicits hunger and causes an increase in feeding activity. Also fall of leptin concentration may be one of the factors responsible for the enhancement of appetite. It has been concluded on the basis of this study that CCK and leptin participates in the short-term regulation of energy balance following exposure to low temperature by potentiating the feeling of hunger.

Cholecystokinin secretion induced by β-conglycinin peptone depends on Gαq-mediated pathways in enteroendocrine cells

Intraduodenal administration of peptone prepared from soybean beta-conglycinin (BconP) stimulates cholecystokinin (CCK) secretion from enteroendocrine cells, and suppresses food intake in rats. However, the sensing mechanism of BconP by CCK-producing cells is unknown. We investigated signal transduction pathways mediating CCK secretion in response to BconP in the murine CCK-producing cell line, STC-1. STC-1 cells were seeded in 48-well culture plates until sub-confluent and CCK secretion was examined under various conditions. CCK concentration was determined by the enzyme immunoassay. BconP dose-dependently induced CCK secretion in STC-1 cells. Treatment with BAPTA-AM, an intracellular Ca2+ chelator, reduced BconP-induced CCK secretion, however, removal of extracellular Ca2+ did not affect the secretory response. Treatment with 2-amino borate (2-APB) reduced CCK releasing responses, suggesting the involvement of IP(3). In addition, BconP failed to induce CCK secretion after treatment with the Galphaq protein inhibitor (YM-254890). These results indicate that Galphaq pathway is responsible for BconP-induced CCK secretion in STC-1 cells, and suggest the involvement of a Galphaq-coupled GPCR(s) in dietary peptide sensing in enteroendocrine cells.

Regulation of early response genes in pancreatic acinar cells: external calcium and nuclear calcium signalling aspects

Nuclear calcium signalling has been an important topic of investigation for many years and some aspects have been the subject of debate. Our data from isolated nuclei suggest that the nuclear pore complexes (NPCs) are open even after depletion of the Ca(2+) store in the nuclear envelope (NE). The NE contains ryanodine receptors (RyRs) and Ins(1,4,5)P(3) receptors [Ins(1,4,5)P(3)Rs], most likely on both sides of the NE and these can be activated separately and independently: the RyRs by either NAADP or cADPR, and the Ins(1,4,5)P(3)Rs by Ins(1,4,5)P(3). We have also investigated the possible consequences of nuclear calcium signals: the role of Ca(2+) in the regulation of immediate early genes (IEG): c-fos, c-myc and c-jun in pancreatic acinar cells. Stimulation with Ca(2+)-mobilizing agonists induced significant increases in levels of expression. Cholecystokinin (CCK) (10 nm) evoked a substantial rise in the expression levels, highly dependent on external Ca(2+): the IEG expression level was lowest in Ca(2+)-free solution, increased at the physiological level of 1 mm [Ca(2+)](o) and was maximal at 10 mm [Ca(2+)](o), i.e.: 102 +/- 22% and 163 +/- 15% for c-fos; c-myc -73 +/- 13% and 106 +/- 24%; c-jun -49 +/- 8% and 59 +/- 9% at 1 and 10 mm of extracellular Ca(2+) respectively. A low CCK concentration (10 pm) induced a small increase in expression. We conclude that extracellular Ca(2+) together with nuclear Ca(2+) signals induced by CCK play important roles in the induction of IEG expression.

Effect of intraperitoneal and intravenous administration of cholecystokinin-8 and apolipoprotein AIV on intestinal lymphatic CCK-8 and apo AIV concentration

CCK and apolipoprotein AIV (apo AIV) are gastrointestinal satiety signals whose synthesis and secretion by the gut are stimulated by fat absorption. Intraperitoneally administered CCK-8 is more potent in suppressing food intake than a similar dose administered intravenously, but the reason for this disparity is unclear. In contrast, both intravenous and intraperitoneally administered apo AIV are equally as potent in inhibiting food intake. When we compared the lymphatic concentration of CCK-8 and apo AIV, we found that neither intraperitoneally nor intravenously administered CCK-8 or apo AIV altered lymphatic flow rate. Interestingly, intraperitoneal administration of CCK-8 produced a significantly higher lymphatic concentration at 15 min than did intravenous administration. Intraperitoneal injection of apo AIV also yielded a higher lymphatic concentration at 30 min than did intravenous administration. Intraperitoneal administration of CCK-8 and apo AIV also resulted in a much longer period of elevated CCK-8 and apo AIV peptide concentration in lymph than intravenous administration. Furthermore, enzymatic activity of dipeptidyl peptidase IV (DPPIV) and aminopeptidase was higher in plasma than in lymph during fasting, and so, satiation peptides, such as CCK-8 and apo AIV in the lymph, are protected from degradation by the significantly lower DPPIV and aminopeptidase activity levels in lymph than in plasma. Therefore, the higher potency of intraperitoneally administered CCK-8 compared with intravenously administered CCK-8 in inhibiting food intake may be explained by both its higher concentration in lymph and the prolonged duration of its presence in the lamina propria.

CCK-58 AND CCK-8 HAVE INDISTINGUISHABLE EFFECTS ON SECRETION AND CELL DEATH IN MURINE PANCREATIC ACINAR CELLS

Introduction: CCK-58 is the main circulating form of cholecystokinin (CCK) and may have different biological actions to CCK-8, used in the majority of experimental studies of CCK action. We have found no differences in Ca2+ signaling evoked by CCK-58 and CCK-8, so investigated whether CCK-58 and CCK-8 have different effects on secretion and cell death. Methods: Comparison of CCK-58 and CCK-8 actions was made using: (1) confocal microscopy of isolated murine pancreatic acinar cells measuring changes in fluorescence from quinacrine (taken up by zymogen granules, lost from the cell after secretion); (2) on-line fluorometric assay with direct perfusion of murine pancreatic tissue to measure amylase activity; (3) confocal microscopy to measure apoptosis (R110-aspartic acid amide) and necrosis (propidium iodide). Results: Physiologically representative concentrations (2 pM, 10 pM) of CCK-58 and CCK-8 evoked typical decreases of quinacrine fluorescence indicative of exocytosis, which did not occur when no stimulus was applied. CCK-58 and CCK-8 (both 10 pM) elicited sustained and reversible increases in amylase secretion of similar magnitude. Supra-maximal (10 nM) CCK-58 or CCK-8 induced similar levels of cell death, with similar relative proportions of apoptosis and necrosis. Conclusion: These data show no significant differences between the actions of CCK-58 and CCK-8 on secretion and cell death. The findings are consistent with our previous data that do not show any difference between the effects of CCK-58 and CCK-8 on isolated murine pancreatic acinar cells.

Effect of the glycemic index of carbohydrates on day-long (10 h) profiles of plasma glucose, insulin, cholecystokinin and ghrelin

Low glycemic index (GI) carbohydrates have been linked to increased satiety. The drive to eat may be mediated by postprandial changes in glucose, insulin and gut peptides. To investigate the effect of a low and a high GI diet on day-long (10 h) blood concentrations of glucose, insulin, cholecystokinin (CCK) and ghrelin (GHR). Subjects (n=12) consumed a high and a low GI diet in a randomized, crossover design, consisting of four meals that were matched for macronutrients and fibre, and differed only in carbohydrate quality (GI). Blood was sampled every 30-60 min and assayed for glucose, insulin, CCK and GHR. The high GI diet resulted in significantly higher glucose and insulin mean incremental areas under the curve (IAUC, P=0.027 and P=0.001 respectively). CCK concentration was 59% higher during the first 7 h of the low GI diet (394+/-95 pmol/l min) vs the high GI diet (163+/-38 pmol/l min, P=0.046), but there was no difference over 10 h (P=0.224). GHR concentration was inversely correlated with insulin concentration (Pearson correlation -0.48, P=0.007), but did not differ significantly between the low and high GI diets. Mixed meals of lower GI are associated with lower day-long concentrations of glucose and insulin, and higher CCK after breakfast, morning tea and lunch. This metabolic profile could mediate differences in satiety and hunger seen in some, but not all, studies.

The effects of selective breeding for differential rates of 50‐kHz ultrasonic vocalizations on emotional behavior in rats

Fifty-kHz ultrasonic vocalizations have previously been shown to be positively correlated with reward and appetitive social behavior in rats, and to reflect a positive affective state. In this study, rats selectively bred for high and low rates of 50-kHz vocalizations as juveniles were tested as adults in a battery of behavioral tests for social/emotional behaviors. We found that animals selectively bred for high rates of 50-kHz vocalizations exhibited more crosses into the center area of the open field apparatus, were more likely to show a preference for a dilute sucrose solution (.8%) compared to tap water, and were less aggressive than randomly bred animals. Conversely, animals bred for low rates of 50-kHz calls produced more fecal boli during both open field testing and "tickling" stimulation, and made less contact with conspecifics in a social interaction test compared to randomly bred animals. We also observed that low line rats have elevated brain levels of cholecystokinin (CCK) in the cortex, which is consistent with literature showing that CCK content in the cortex is positively correlated with rates of aversive 22-kHz USVs. Conversely, high line animals had elevated levels of met-enkephalin in several brain regions, which is consistent with the role of endogenous-opioids in the generation 50-kHz USVs and positive affect. These results suggest that animals bred for high rates of 50-kHz may show a stress resilient phenotype, whereas low line rats may show a stress prone phenotype. As such these animals could provide novel insights into the neurobiology of emotion.

Effect of ileal fat perfusion on satiety and hormone release in healthy volunteers

The ileal brake is a feedback mechanism activated by nutrients, especially fat, with marked effects on satiety. The effects of low doses of ileal fat on satiety are largely unknown. We therefore studied the effect of ileal vs oral delivery of low doses of fat on satiety and gut peptide secretion. Randomized, single-blind crossover design. Sixteen healthy, normal-weight volunteers (6 male; mean age 26 years, mean body mass index 22.4). Participants were intubated with a 290-cm-long nasoileal tube and consumed, on 3 consecutive days, either a liquid breakfast with 3 g fat followed by an ileal placebo infusion at t=105-150 min (treatment C) or a fat-free liquid breakfast followed by an ileal infusion of either an emulsion of 3 g (treatment 13 g) or 9 g (treatment 19 g) fat (safflower oil). Satiety parameters by visual analog scales and plasma concentrations of CCK and PYY. C significantly increased satiety and CCK secretion compared with the fat-free breakfast. Ileal fat perfusion of both 3 and 9 g 13 g and 19 g) significantly increased satiety during and after fat perfusion, without differences in satiety between 13 g and 19 g. During ileal fat infusion, CCK increased dose dependently, whereas PYY concentrations increased significantly only after 9 g of fat. Secretion of CCK but not of PYY correlated to satiety levels. Postprandial satiety following a liquid breakfast can be effectively and significantly increased by small amounts (as little as 3 g) of fat perfused into the ileum. Ileal fat dose-dependently increased CCK but not PYY secretion. The satiating effect of ileal fat may be partly mediated by CCK.

The Growth-promoting Effect of Tetrabasic Zinc Chloride is Associated with Elevated Concentration of Growth Hormone and Ghrelin

An experiment was conducted to investigate the mechanism for the effect of tetrabasic zinc chloride (TBZC) in enhancing growth performance of weanling piglets. Gut-brain peptides play an important role in the regulation of growth and appetite in animals. This study evaluated the effects of TBZC on blood concentrations of growth hormone (GH), ghrelin, insulin-like growth factor-I (IGF-I), cholecystokinin (CCK) and neuropeptide Y (NPY). Seventy-two weanling piglets (LandracexLarge White) with an initial body weight (BW) of 6.7±0.16 kg and aged 24±1 days were assigned to three dietary treatments: i) control diet without TBZC supplement, ii) the control diet supplemented with 2,000 mg Zn from TBZC/kg and iii) TBZC-supplemented diet pair-fed with respect to the control diet. Each treatment had six replications (pens) of four piglets. At the end of a 14-d experimental period, piglets were weighed and feed consumption was measured, and blood samples were collected for assays of GH, ghrelin, IGF-I, CCK and NPY concentrations. The inclusion of TBZC in the diet increased average daily gain (p 0.05) serum IGF-I and plasma NPY and CCK concentrations. Pair-fed piglets had lower (p 0.05) differ from Control piglets. These data indicated that TBZC elevated the concentration of ghrelin and GH. This observation may partly explain the beneficial effects of TBZC on growth performance of weanling piglets.

Functional Dyspepsia Is Associated With a Greater Symptomatic Response to Fat But Not Carbohydrate, Increased Fasting and Postprandial CCK, and Diminished PYY

In patients with functional dyspepsia (FD), symptoms are frequently triggered, or exacerbated, by fatty foods. We hypothesized that in FD patients, a high-fat (high-FAT) meal would induce more symptoms than a high-carbohydrate (high-CHO) meal, associated with an altered secretion of cholecystokinin (CCK), peptide-YY (PYY), and ghrelin and an increased antral size, when compared to healthy subjects (HS). FD symptoms, appetite perceptions, plasma hormones, and antral area were measured in 8 FD patients and 8 HS on three separate days after the ingestion of high-CHO or high-FAT (500 kcal/400 g) meals, or a low-nutrient control (180 kcal/400 g); the energy intake was quantified 60 min later. Nausea (P < 0.01) and pain (P= 0.05) were greater in FD after the high-FAT, when compared to high-CHO and control meals and in HS. Discomfort was greater after all meals in FD when compared to HS (P < 0.05). Fasting CCK and stimulation of CCK by the high-FAT (P < 0.01) meal were greater in FD, while fasting and postprandial PYY were lower (P < 0.001) in FD than in HS, with no differences in fasting, or postprandial, plasma ghrelin between FD and HS. Fasting antral area was greater in FD (P < 0.05), with no differences postprandially between FD and HS. There were no differences in the energy intake between the two groups. In FD patients: (a) a high-FAT meal induces more symptoms than an isocaloric high-CHO meal, and (b) fasting and postprandial plasma CCK concentrations are greater and PYY concentrations are less. Our findings have important implications for the development of diet-based therapies for the treatment of FD.

Neurotensin and cholecystokinin depress motility in isolated Lumbricus terrestris crop-gizzard preparations

The effects of neurotensin (NT) and cholecystokinin (CCK) were studied on isolated crop-gizzard preparations of Lumbricus terrestris suspended in a smooth muscle organ bath. Changes in the amplitude and frequency of contractions associated with spontaneous motility were observed in response to neurotransmitters known to have an excitatory effect (acetylcholine) and an inhibitory effect (serotonin); and to the hormones NT and CCK, which in vertebrate models have both been shown to inhibit gastric motility. The overall contractile amplitude and frequency of crop-gizzard contractions were decreased in response to increasing concentrations of NT and CCK. In general, both hormone-induced responses were similar when compared at equal molar concentrations. Cholecystokinin, however, did exhibit a greater reduction in contractile frequency than NT. It is speculated that possible desensitization of earthworm NT-receptors to higher hormone concentrations resulted in a depressed maximal response in the concentration–response curve. Despite that possibility, the overall hormonal inhibition was statistically significant. These results infer that NT- and CCK-induced inhibition of crop-gizzard motility may have a modulatory role in the transport of nutrients and overall efficiency of worm metabolism.

Reproducibility of energy intake, gastric emptying, blood glucose, plasma insulin and cholecystokinin responses in healthy young males

Gastric emptying, as well as intragastric meal distribution, and gastrointestinal hormones, including cholecystokinin (CCK), play an important role in appetite regulation. The evaluation of gastrointestinal factors regulating food intake is commonly performed in healthy, lean, young male participants. It has, however, been suggested that there is a marked interindividual variability in the effects of nutrient 'preloads' on energy intake in this group. Whether there is significant intraindividual variation in acute energy intake after a nutrient preload, and, if so, how this relates to day-to-day differences in gastric emptying and gastrointestinal hormone release, is unclear. The purpose of the present paper is to evaluate the hypothesis that energy intake after a nutrient preload would be reproducible and associated with reproducible patterns of gastric emptying, intragastric distribution and gastrointestinal hormone release. Fifteen healthy men (age 25 (sem 5) years) consumed a glucose preload (50 g glucose in 300 ml water; 815 kJ) on three occasions. Gastric emptying and intragastric meal distribution (using three-dimensional ultrasound), blood glucose, plasma insulin and CCK concentrations and appetite perceptions were evaluated over 90 min, and energy intake from a cold buffet-style meal was then quantified. Energy intake was highly reproducible within individuals between visits (intraclass correlation coefficient, ri = 0.9). Gastric emptying, intragastric meal distribution, blood glucose, plasma insulin and CCK concentrations and appetite perceptions did not differ between visits (ri>0.7 for all). In healthy males, energy intake is highly reproducible, at least in the short term, and is associated with reproducible patterns of gastric emptying, glycaemia, insulinaemia and CCK release.

Does Chronic Ethanol Intake Cause Chronic Pancreatitis?

To demonstrate the relationship between prolonged alcohol intake and chronic pancreatitis. Wistar rats were fed diet containing 25% concentration (vol/vol) of ethanol for 6 months. Cholecystokinin (CCK) was quantified by radioimmunoassay. Immunohistochemistry was used to detect alpha-smooth muscle actin, cyclooxygenase 2, and toll-like receptor 4 in rat pancreas. Western-blot was used to quantitatively determine the expression of nuclear factor kappaB and the above inflammatory markers. Pancreatic collagen content was quantified by measuring OH-proline. Superoxide dismutase was measured by colorimetric method. In contrast to the control group, there was little histological change in pancreatic tissue but obvious ultrastructural changes in acinar cells of the ethanol group. Cholecystokinin, amylase, and lipase were found reduced in the ethanol group. Chronic ethanol intake did not elicit any change in the expression of alpha-smooth muscle actin, cyclooxygenase 2, toll-like receptor 4, nuclear factor kappaB, pancreatic collagen, and superoxide dismutase. Long-term alcohol consumption did not cause chronic pancreatitis but impaired exocrine pancreatic function. The mechanism behind it could be associated with decreased output of intestinal CCK and lower concentration of pancreatic CCK. Furthermore, the nonoxidative pathway of ethanol metabolism was probably involved in it.

DISCREPANCY BETWEEN PANCREATIC PROTEIN SECRETION AND CCK RELEASE IN RESPONSE TO BILE-PANCREATIC JUICE DIVERSION IN THE HYPERTROPHIED RAT PANCREAS INDUCED BY SYNTHETIC TRYPSIN INHIBITOR

Pancreatic exocrine secretion in conscious rats is mainly regulated by protease activities in the proximal intestine (luminal feedback regulation).1 Decrease in protease activities by ingestion of trypsin inhibitors (TI)s or diversion of bile-pancreatic juice (BPJ) stimulates pancreatic secretion2 and produces pancreatic hypertrophy via CCK release. Since CCK releasing factor, LCRF was purified from rat intestine,3 we determined whether the levels of LCRF, CCK, and protein secretion were synchronized to one another. Changes in pancreatic secretion, plasma CCK levels, and luminal LCRF contents produced by 2- and 4-h BPJ diversion, were determined in rats with 7-day TI treatment, and compared with controls. A diet containing 0.1% synthetic TI (ONO-3402) and a standard diet (CE-2) were fed in Wistar male rats for 7 days. After 7 day-treatment, the pancreatic wet weight was significantly higher in TI treated rats than the controls. For the experiments, on the third day of the feeding, rats were prepared with cannulas draining BPJ separately, and with a duodenal cannula and with an external jugular vein cannula. On the 7th day of the feeding, after 90 min of basal secretion with returning BPJ, BPJ were diverted. Changes in pancreatic secretions of fluid and protein were determined. After 2- and 4-h BPJ diversion, rats were sacrificed. Samples of 3-4 ml of blood were withdrawn through the venous cannula to measure plasma CCK concentrations. The proximal quarter of the small intestine was removed to measure LCRF content. The levels of LCRF and CCK were parallel (Fig. 1). Pancreatic protein secretion was higher in rats treated with TI than in controls throughout the experimental period. The plasma CCK and luminal LCRF content 4-h after BPJD was significantly lower in rats treated with TI than in controls. The hypertrophied pancreas may require a smaller dose of CCK to increase protein secretion.FIGURE 1: Changes in plasma CCK concentrations, LCRF content, and pancreatic protein secretion after 4-h BPJ diversion. *significantly different from the control values. TI; trypsin inhibitor. The numbers in the parentheses are the number of animals.

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.