Adaptation to high-fat diet reduces inhibition of gastric emptying by CCK and intestinal oleate

Rats maintained on low-fat (LF) or high-fat (HF) diets were fitted with gastric cannulas and duodenal catheters. Intraperitoneal injection of 0.250-2.0 microg/kg cholecystokinin (CCK) significantly inhibited gastric emptying of a 5-ml NaCl load in LF rats by 26.2-55. 1% compared with emptying after vehicle injection. By contrast, CCK-induced inhibition of gastric emptying was significantly less in HF rats given the same CCK doses (10.0-31.7% inhibition over the same CCK dose range). A 20-min intraduodenal infusion of oleate (0.03 or 0.06 kcal/ml) also resulted in significant inhibition of gastric emptying in LF rats (24 and 89%, respectively). Oleate-induced inhibition of gastric emptying was significantly attenuated in rats maintained on the HF diet (2 and 56%, respectively). Unlike CCK injections or oleate infusion, intraduodenal maltotriose infusion inhibited gastric emptying to a similar degree in LF and HF rats (77 and 78%, respectively). These results indicate that feeding HF diets diminishes the enterogastric inhibition of gastric emptying by intestinal oleate and diminishes the ability of CCK to inhibit gastric emptying.     

Performance of piglets in response to the standardized ileal digestible phenylalanine and tyrosine supply in low-protein diets

Reducing the CP level of the diet allows for a reduction in N excretion without limiting performance as long as the amino acid (AA) requirements are covered. The availability of crystalline AA has permitted for a considerable reduction in the CP level of diets, practically used in pig nutrition. The adoption of low CP diets and the extent to which the CP content can be reduced further depends on the knowledge of the minimum levels of indispensable AA that maximize growth. The standardized ileal digestible (SID) Phe : Lys and Tyr : Lys requirements and the possibility to substitute Tyr by Phe have never been studied in piglets. The objectives of this study were to estimate these requirements in 10 to 20 kg pig as well as to determine the extent to which Phe can be used to cover the Tyr requirement. In three dose–response studies, six pigs within each of 14 blocks were assigned to six low CP diets (14.5% CP) sub-limiting in Lys at 1.00% SID. In experiment 1, the SID Phe : Lys requirement estimate was assessed by supplementing a Phe-deficient diet with different levels of l-Phe to attain 33%, 39%, 46%, 52%, 58%, and 65% SID Phe : Lys. Because Phe can be used for Tyr synthesis, the diets provided a sufficient Tyr supply. A similar approach was used in experiment 2 with six levels of l-Tyr supplementation to attain 21%, 27%, 33%, 39%, 45% and 52% SID Tyr : Lys. Phenylalanine was supplied at a level sufficient to sustain maximum growth (estimated in experiment 1). The SID Phe : Lys and SID Tyr : Lys requirements for maximizing daily gain were 54% and 40% using a curvilinear-plateau model, respectively. A 10% deficiency in Phe and Tyr reduced daily gain by 3.0% and 0.7%, respectively. In experiment 3, the effect of the equimolar substitution of dietary SID Tyr by Phe to obtain 50%, 57%, and 64% SID Phe : (Phe+Tyr) was studied at two limiting levels of Phe+Tyr. From 57% to 64% SID Phe : (Phe+Tyr), performance was slightly reduced. In conclusion, it is recommended not to use a Phe+Tyr requirement in the ideal AA profile but rather use a SID Phe : Lys of 54% and a SID Tyr : Lys of 40% to support maximal growth.     

Adaptation to low-protein diet increases inhibition of gastric emptying by CCK

Chronic nutritional disorders such as protein malnutrition are associated with delayed gastric emptying and increased postprandial cholecystokinin (CCK) levels. This study investigated the mechanisms involved in gastric emptying adaptation to low-protein diet. Two groups of 12 rats were adapted to a low-protein (LPD) or standard diet (SD) for 3 weeks. As compared to rats fed a SD, in rats adapted to a LPD gastric emptying was delayed, whereas postprandial CCK levels were increased. LPD enhanced antral muscle contractile response to CCK and cerulein without altering response to acetylcholine. This increased contractility was associated with up-regulation of CCK-A receptor mRNA levels in antral muscle. Our data suggest that modulation of gastric emptying after adaptation to a low-protein diet involves up-regulation of both CCK-A receptors and CCK-induced contraction of antral smooth muscle.     

High fat maintenance diet attenuates hindbrain neuronal response to CCK

Rats maintained on a high fat diet reduce their food intake less in response to exogenous cholecystokinin (CCK) than rats maintained on a low fat diet. In addition, inhibition of gastric emptying by CCK is markedly attenuated in rats maintained on a high fat diet. Both inhibition of food intake and gastric emptying by CCK are mediated by sensory fibers in the vagus nerve. These fibers terminate on dorsal hindbrain neurons of the nucleus of the solitary tract and area postrema. To determine whether diet-induced changes in the control of feeding and gastric emptying are accompanied by altered vagal sensory responsiveness, we examined dorsal hindbrain expression of Fos-like immunoreactivity (Fos-li) following intraperitoneal CCK injection of rats maintained on high fat or low fat diets. Following CCK, there were numerous Fos-li nuclei in the area postrema and in the commissural and medial subnuclei of the nucleus of the solitary tract of rats maintained on a low fat diet. However, Fos-li was absent or rare in the brains of rats maintained on a high fat diet. These data suggest that the vagal sensory response to exogenous CCK is reduced in rats maintained on a high fat diet. Our results also are consistent with our previous findings that CCK-induced reduction of food intake and gastric emptying are both attenuated in rats maintained on a high fat diet. In addition our results support the hypothesis that attenuation of CCK-induced inhibition of food intake and gastric emptying may be due to diet-induced diminution of vagal CCK responsiveness.     

Effect of phenylalanine on pancreatic amylase secretion in chicks (Gallus domesticus).

1. Effect of phenylalanine (Phe) on pancreatic amylase secretion in growing chicks was investigated in four experiments. 2. In Experiment 1, birds were injected through a wing vein with 0.25 ml Phe at 0, 0.1, 0.5, 2.5 and 12.5 mM in physiological saline. No significant difference was observed in amylase secretion among treatments. 3. Effect of various concentrations of Phe with cholecystokinin (CCK, 0.31 Crick unit) on amylase secretion was investigated in Experiment 2. Amylase secretion increased with time, although no significant effect was detected in Phe treatment. 4. Efficacy of Phe and tyrosine (Tyr) injection with CCK on amylase secretion was compared. There was no significant difference between Phe and Tyr treatments. 5. Birds were injected intraperitoneally with dl-p-chlorophenylalanine (p-CP), which is an inhibitor of phenylalanine hydroxylase, or saline 1 day before the collection of pancreatic amylase in Experiment 4. Both chicks showed increased amylase secretion with CCK (0.31 Crick unit), whereas the response was at a drastically reduced rate in chicks with the p-CP treatment.     

Protective effect of long term high fiber diet consumption on rat exocrine pancreatic function after chronic ethanol intake

The effects of ethanol administration on exocrine pancreas have been widely studied, but little is known about the effect of dietary fiber in combination with chronic ethanol on exocrine pancreatic function. The aim of this work was to examine the chronic effects of a high fiber diet, ethanol ingestion, and a combination of both on the function of the rat exocrine pancreas. Four groups of rats were fed for six months the following diets: 1.- NW: standard laboratory diet; 2.- FW: high fiber diet (15% cellulose); 3.- NE: standard laboratory diet and 20% ethanol in the drinking water; and 4.- FE: high fiber diet and 20% ethanol. Cholecystokinin (CCK) and acetylcholine (Ach) effects on amylase release and intracellular calcium mobilization in pancreatic acini were studied. In rats fed a 20% ethanol (NE), both the basal amylase release and the basal [Ca(2+)](i) were significantly increased; nonetheless, CCK and Ach-induced amylase release were significantly reduced compared with control rats. Ach- but not CCK-stimulated [Ca(2+)](i) increase in NE rats was significantly decreased compared with NW. In rats fed a combination of ethanol and a high fiber diet (FE) all the parameters under study were not significantly affected compared to control rats (NW). In conclusion, high fiber consumption does not alter the function of the exocrine pancreas. However, it ameliorates the deleterious effect of chronic ethanol consumption on pancreatic amylase secretion and, at least partially, reverses the ethanol-induced alterations on [Ca(2+)](i) in the rat exocrine pancreas.     

Role of tyrosine sulfation and serine phosphorylation in the processing of procholecystokinin to amidated cholecystokinin and its secretion in transfected AtT-20 cells

Mammalian procholecystokinin (pro-CCK) is known to have three sulfated tyrosine residues, one of which is present in the CCK 8 moiety and two additional residues present in the carboxyl-terminal extension. In the present study, inhibition of tyrosine sulfation by sodium chlorate decreased the secretion of processed CCK 8 in CCK-expressing endocrine cells in culture. It was then demonstrated that when each of these tyrosines individually, as well as all three together, was mutated to phenylalanine and expressed in endocrine cells, CCK was still processed and secreted. However, the amount of CCK secreted varied with the type of mutation. Substitution of Phe to Tyr in CCK 8 reduced the quantity of secreted CCK 8 by 50%, and when all the sulfated Tyr were mutated to Phe the quantity of secreted CCK was reduced by about 70%, similar to what is observed with chlorate treatment. Changing of the putative phosphorylation site serine to alanine does not affect the processing. Serine phosphorylation at this site may play a functional role in regulatory events. Our results demonstrate that tyrosine sulfation alters the amount of secretion but is not an absolute requirement for the processing and secretion of CCK in this cell line. Tyrosine sulfation of CCK may still be important for its solubility, stabilization, and/or functional interaction.     

Studies on limiting essential amino acids in grieves as source of dietary protein for rainbow trout (oncorhynchus mykiss)

Diets were computed to contain equal concentrations of digestible crude protein either of wheat gluten (diet 1) or of grieves (diets 2–8). Per kg dry diet, 41 g crystalline amino acids were supplemented. All diets contained at least 1.2 g Lys per MJ digestible energy (DE). In diet 2, ratios of Met + Cys, Trp, Leu, Ile and Phe to Lys were about equal to those in diet 1. In each of diets 3–7, one of the respective amino acids, in diet 8 all five were replaced by Glu in the supplemented mixture of amino acids.

Each diet was fed to triplciate groups of 20 trout during a trial lasting 66 days. Trout fed the diet containing wheat gluten consumed more dry matter and showed higher growth rates as well as higher protein contents in their gained body mass than trout fed diets based on grieves. Supplementing Met plus Trp significantly improved dry matter intake, growth rate and protein content of gain, though not to the level of trout fed the wheat gluten diet, whereas Leu, Ile and Phe showed no such effect. When grieves were not supplemented with both Met and Trp, gain in body mass contained significantly more lipids. DE required per kg gain by trout fed wheat gluten, grieves + Met + Trp or grieves without supplementation of Met and Trp was 20.1, 21.2 and 29.9 MJ, respectively.     

Effect of partial dehulling of two- and six-row barley varieties on precaecal digestibility of amino acids in pigs

Five barrows (German Landrace; initial BW 58 kg, final BW 80 kg) fitted with an ileo-rectal anastomosis were used to determine the effect of partial dehulling and addition of barley hulls of two- and six-row barley varieties on the precaecal digestibility (pD) of CP and amino acids. The following diets were provided according to a standardized diet formulation and tested in seven consecutive periods (repeated group-period design): two-row barley (TRB) + casein (C), dehulled TRB + C, TRB + C + 10% hulls, six-row barley (SRB) + C, dehulled SRB + C, SRB + C + 1% hulls, and wheat starch + C. The diets were supplied at daily rates of 79-86 g DMI x kg BW(-0.75) in barley containing diets and at 49 g DMI x kg BW(-0.75) in the casein diet. The digestibility of amino acids in barley varieties was determined by the difference method (casein as basal diet) using quantitative digesta collection. In both varieties of barley the pD of CP and amino acids did not differ. The pD of CP was unchanged in regard to the treatments in both barley varieties. Due to dehulling in TRB the pD was improved significantly for most indispensable amino acids and in SRB for Met and Cys. Addition of 10% hulls to TRB led to equivalent pD of Arg, His, Leu, Tyr, and Trp compared to TRB, but the pD of Lys, Phe, Thr and Val was significantly decreased below the levels of TRB. Addition of even 1% hulls to SRB impaired the pD of Lys below the level in SRB. In conclusion, addition of barley hulls to pig diets impairs amino acids absorption in the small intestine. The pD values, measured under standardized experimental conditions (without a correction using basal endogenous amino acids), are similar to the values of true digestibility published by NRC (1998).     

Effects of juice from Morinda citrifolia (Noni) on gastric emptying in male rats

The effects of juice from Morinda citrifolia (noni) on gastric emptying, gastrointestinal transit, and plasma level of cholecystokinin (CCK) in rats were studied. Male rats were given noni by gavage at levels of 0.25, 1, or 4 ml/kg once per day for one or 7 days. The rats in the control group were given water, while the rats in the experimental group were fasted overnight before measurement of gastrointestinal motility. Gastrointestinal motility was assessed in rats 15 min after intragastric instillation of a test meal containing charcoal (10%) and Na251CrO4 (0.5 microCi/ml). Gastric emptying was determined by measuring the amount of radiolabeled chromium contained in the small intestine as a percentage of the initial amount received. Then, gastrointestinal transit was evaluated by calculating the geometric center of distribution of the radiolabeled marker. Finally, blood samples were collected for measurement of CCK by radioimmunoassay. The administration of noni at 0.25 ml/kg, but not at 1 ml/kg and 4 ml/kg, for 1 day significantly inhibited gastric emptying. In contrast, gastric emptying was significantly inhibited by oral noni (0.25, 1, or 4 ml/kg) for 7 days. Intraperitoneal injection of lorglumide (5 or 10 mg/kg), a selective CCK1 receptor antagonist, effectively attenuated the noni-induced inhibition of gastric emptying. The intestinal transit and body weight, food intake, water intake, urine volume as well as feces weight were not altered by the administration of noni either acutely or chronically, but the administration of oral noni (1 ml/kg) for 7 days increased the level of plasma CCK in male rats. These results suggest that oral noni inhibits gastric emptying in male rats via a mechanism involving stimulation of CCK secretion and CCK1 receptor activation.     

5-HT3 receptors participate in CCK-induced suppression of food intake by delaying gastric emptying

Serotonin type 3 (5-HT(3)) receptors have been shown to participate in the negative-feedback control of food intake. We previously reported that cholecystokinin (CCK)-induced suppression of food intake is partly mediated through 5-HT(3) receptors when rats were tested on a preferred liquid diet, but whether such an effect occurs when they are tested on a solid maintenance diet is unknown. In the present study, we examined the effects of ondansetron, a selective 5-HT(3) antagonist, on CCK-induced suppression of solid chow intake. Intraperitoneal administration of ondansetron significantly attenuated 30- and 60-min CCK-induced reduction of food intake, with suppression being completely reversed by 120 min. It is not known whether 5-HT(3) receptors directly mediate CCK-induced satiation or whether their participation depends on CCK acting as part of a feedback cascade to inhibit ongoing intake. Because CCK-induced inhibition of sham feeding does not depend on additive gastric/postgastric-feedback signals, we examined the ability of ondansetron to reverse CCK-induced satiation in sham-feeding rats. Ondansetron did not attenuate reduction of sham feeding by CCK, suggesting that ondansetron does not directly antagonize CCK-satiation signals. CCK suppresses real feeding through a delay in gastric emptying. Ondansetron could attenuate CCK-induced reduction of food intake by reversing CCK-induced inhibition of gastric emptying. We found that blockade of 5-HT(3) receptors attenuates CCK-induced inhibition of gastric emptying of a solid meal, as well as saline and glucose loads. We conclude that 5-HT(3) receptors mediate CCK-induced satiation through indirect mechanisms as part of a feedback cascade involving inhibition of gastric emptying.     

Variation of glutathione level and synthesis activity in chick liver due to selenium and vitamin E deficiencies

Chicks were fed an amino acid mixture-based diet (basal diet) or one supplemented with selenium (Se, 0.2 micrograms/g as Na2SeO3) and/or vitamin E (100 micrograms/g as alpha-tocopherol). The group receiving the basal diet devoid of Se and vitamin E showed a tendency to grow slowly, but not significantly so, compared to the non-deficient control and manifested a symptom of exudative diathesis after the feeding period of 4 weeks. Supplementation of the basal diet with Se or vitamin E prevented the deficiency symptoms in the chicks. The hepatic GSH level and GSH synthesis activity were about three times as much in the Se- and vitamin E-deficient group as in the control. This was also the case for in vivo sulfur incorporation into hepatic GSH for 10 h post-injection with [35S]methionine. The increased level of GSH may partly compensate the hepatocytes for peroxidative damage.     

Phenylalanine and tyrosine kinetics in compensated liver cirrhosis: effects of meal ingestion

We explored the mechanism(s) of increased aromatic amino acids concentrations in liver cirrhosis using phenylalanine (Phe) and tyrosine (Tyr) isotope infusions in male patients with compensated cirrhosis (five in Child Class A, three in B) and in eight matched healthy controls, in both postabsorptive and fed states. After a baseline period, a standard liquid mixed meal was fed continuously over 4 h. Both a "plasma" and an intracellular model were employed. In the patients, steady-state Phe and Tyr concentrations were approximately 30-50% greater, and rates of Phe appearance (Ra) (plasma model), Tyr Ra, and Phe hydroxylation (Hy; both models) were approximately 25 to >100% greater than in controls in both states. Meal ingestion increased (P<0.05 or less vs. basal) Phe and Tyr concentrations, Phe and Tyr Ra, Phe Hy, and % Tyr Ra not deriving from Hy in both groups. Hy and Tyr Ra remained>50% greater (P<0.04 to P<0.01) in patients, whereas Phe Ra was more modestly increased. Phe utilization for protein synthesis increased similarly in both groups. Tyr clearance was normal, whereas Phe clearance tended to be lower (P=0.09, intracellular model) in the patients. In summary, in compensated liver cirrhosis studied under fasted and fed states, 1) Tyr Ra is increased; 2) Phe Hy and Phe Ra (plasma model) are increased; 3) Tyr clearance is normal; and 4) Phe clearance is slightly decreased. In conclusion, in cirrhosis increased total tyrosine Ra and hydroxylation contribute to fasting and postmeal hypertyrosinemia, whereas the mechanism(s) responsible for the hyperphenylalaninemia may include both increased production and decreased disposal.     

Leptin inhibits gastric emptying in rats: role of CCK receptors and vagal afferent fibers

Leptin regulates energy homeostasis and body weight by balancing energy intake and expenditure. It was recently reported that leptin, released into the gut lumen during the cephalic phase of gastric secretion, is capable of initiating intestinal nutrient absorption. Vagal afferent neurons also express receptors for both CCK and leptin, which are believed to interact in controlling food intake. The present study was undertaken to investigate the central and peripheral effects of leptin on gastric emptying rate. Under anesthesia, male Sprague-Dawley rats (250-300 g) were fitted with gastric Gregory cannulas (n=12) and some had additional cerebroventricular cannulas inserted into their right lateral ventricles. Following recovery, the rate of gastric emptying of saline (300 mOsm/kg H(2)O) was determined after instillation into the gastric fistula (3 ml, 37 degrees C, containing phenol red, 60 mg/l as a non-absorbable dilution marker). Gastric emptying rate was determined from the volume and phenol red concentrations recovered after 5 min. Leptin, injected intraperitoneally (i.p.; 10, 30, 60, 100 microg/kg) or intracerebroventricularly (i.c.v.; 5, 15 microg/rat) 15 min before the emptying, delayed gastric emptying rate of saline at the dose of 30 microg/kg or 15 microg/rat (p<0.001). When CCK(1) receptor blocker L-364,718 (1 mg/kg, i.p.), CCK(2) receptor blocker L-365,260 (1 mg/kg, ip) or adrenergic ganglion blocker bretylium tosylate (15 mg/kg, i.p.) was administered 15 min before ip leptin (30 microg/kg) injections, leptin-induced delay in gastric emptying was abolished only by the CCK(1) receptor blocker (p<0.001). However, the inhibitory effect of central leptin on gastric emptying was reversed by adrenergic blockade, but not by either CCK antagonists. Our results demonstrated that leptin delays gastric emptying. The peripheral effect of leptin on gastric motility appears to be mediated by CCK(1) receptors, suggesting the release of CCK and the involvement of vagal afferent fibers. On the other hand, the central effect of leptin on gastric emptying is likely to be mediated by adrenergic neurons. These results indicate the existence of a functional interaction between leptin and CCK receptors leading to inhibition of gastric emptying and short-term suppression of food intake, providing an additional feedback control in producing satiety.     

Orlistat reduces gallbladder emptying by inhibition of CCK release in response to a test meal

BACKGROUND AND AIMS: Orlistat is a covalent inhibitor of digestive lipase derived from lipstatin, the natural product of Streptomyces toxytricini. By blocking the active site of intestinal lipase, orlistat inhibits hydrolysis of dietary triglycerides and thus reduces the intestinal lipid absorption. It is uncertain whether intestinal inhibition of lipase by orlistat also interferes with nutrient-induced CCK release from intestinal I-cells. The aim of the present study was therefore to assess whether oral administration of orlistat inhibits CCK release in response to a test meal and thus causes impaired gallbladder emptying. METHODS: 22 healthy volunteers were given a test meal consisting of 200 ml dairy cream and two teaspoons of chocolate powder (552 kcal=2328 kJ; 56.0 g fat; 5.2 g proteins, 6.6 g carbohydrates), with and without oral application of 120 mg orlistat. Gallbladder volume was determined by ultrasound before and 5, 10, 20, 30 and 40 min after meal ingestion. In parallel, a venous blood sample was collected for the measurement of bioactive CCK. CCK activity was assessed using a bioassay with isolated rat pancreatic acini cells. RESULTS: Oral administration of orlistat significantly impairs gallbladder emptying. After ingestion of the test meal the gallbladder contracted by 78.5% in the control group, whereas the test group with orlistat only showed a contraction of 45.7% (p<0.01). Maximal contraction was reached after 35 to 40 min, the maximal gallbladder emptying was delayed up to 10 min by orlistat. Orlistat induced a significant reduction of bioactive CCK levels in response to a test meal (CCK(max) with orlistat=4.1 pmol/l; CCK(max) without orlistat=7.8 pmol/l). CCK levels were reduced by 47% and the onset of maximal CCK secretion was delayed up to 10 min. CONCLUSION: The inhibition of intestinal lipolytic activity by orlistat results in reduced gallbladder emptying through inhibition of meal-mediated CCK release. We therefore hypothesize that impaired gallbladder motility may represent a risk factor in chronic treatment of severe obesity using orlistat.     

Exogenous melatonin delays gastric emptying rate in rats: role of CCK2 and 5-HT3 receptors.

Pineal hormone melatonin is proposed as a potential treatment for severe sleep disturbances, and various gastrointestinal disorders. It was shown that melatonin increases intestinal motility and influences the activity of myoelectric complexes of the gut. The aim of the study was to evaluate the mechanisms of the effect of exogenous melatonin on gastric emptying rate. Male Sprague-Dawley rats were fitted with gastric cannulas under anesthesia. The rate of gastric emptying of saline was determined after instillation into the gastric fistula, from the volume and phenol red concentrations recovered after 5 min. Melatonin injected intraperitoneally (ip; 0.001-100 mg/kg) delayed gastric emptying rate of saline at 3 and 10 mg/kg doses. When administered ip 15 min before melatonin (10 mg/kg) injections, CCK2 (L-365,260, 1 mg/kg) or 5-HT3 receptor (ramosetrone, 50 microg/kg) blockers abolished melatonin-induced delay in gastric emptying rate, while the blockade of sympathetic ganglia (bretylium tosylate, 15 mg/kg) significantly reduced the delay in gastric emptying rate. CCK1 receptor blocker (L-364,718, 1 mg/kg) had no significant effect on the delaying action of melatonin. Our results indicate that pharmacological doses of melatonin delay gastric emptying via mechanisms that involve CCK2 and 5-HT3 receptors. Moreover, it appears that exogenous melatonin inhibits gastric motility in part by activating sympathetic neurons.     

Gastric emptying in response to IAPP and CCK in rats with subdiaphragmatic afferent vagotomy

In the subdiaphragmatic vagal deafferentation procedure (SDA), the afferent fibers of the vagus are surgically severed unilaterally where they enter the brain stem. The technique includes a subdiaphragmal truncal vagotomy performed on the contralateral side. This procedure has been used to study the control of food intake, but it has not been used previously to investigate the role of vagal afferent fibers in the control of gastric emptying (GE). The current experiment studied the effect of SDA on the inhibition of GE by islet amyloid polypeptide (IAPP or amylin) and cholecystokinin (CCK) in awake, unrestrained rats with gastric cannulas. The experimental group underwent subdiaphragmatic vagal deafferentation; the control group had sham operations. All rats received 20-min intravenous infusions of IAPP (1, 3, 9, 27, and 81 pmol/kg/min), CCK (3, 30 and 90 pmol/kg/min), and normal saline in random order. Gastric emptying of saline was measured by the phenol red method during the last 5 min of each infusion period. CCK dose-dependently inhibited gastric emptying in both the control and SDA animals. The inhibition of GE by CCK was significantly attenuated by SDA (p<0.01). IAPP also inhibited gastric emptying dose-dependently, but the difference between the SDA and control groups was not significant. The current experiment, which used a different methodology than previous studies, provides support for the hypothesis that the inhibition of gastric emptying by CCK, but not by IAPP, is mediated partly by afferent vagal fibers.     

Effect of dietary vitamin B6 contents on antibody production

When mice were placed on diets extreme deficient in vitamin B6, ovalbumin-dependent antibody productions (IgE, IgG1, IgG2a) were significantly suppressed, and alanine aminotransferase activity in the liver was also significantly decreased. In the case of pyridoxine excess (6 mg% = about ten times standard amount) in a 70% casein diet, ovalbumin-dependent antibody productions were also considerably suppressed. These responses were weaker in a low casein (5%) or normal casein (20%) diet than in a 70% casein diet. The administration of high doses of pyridoxine (6 mg%) resulted in the suppression of hepatic cathepsin B activity. Therefore, we conclude that ovalbumin-dependent antibody productions (IgG1, IgE) were suppressed by pyridoxine excess diet (6 mg%), because hepatic cathepsin B activity was suppressed by the excess pyridoxine in diet.     

Ileal and total tract nutrient digestibility in blue foxes (Alopex lagopus) fed extruded diets containing different protein sources

This study compared apparent ileal and total tract digestibility of macronutrients and amino acids in blue foxes (Alopex lagopus) fed dry extruded diets. The control diet contained fish meal as the main protein source, while in the other diets 50% of the fish meal protein was replaced by not de-hulled solvent-extracted soybean meal, meat meal or bacterial protein meal. Ileal digestibility was obtained with animals modified with ileorectal anastomosis (IRA method). There were no significant differences in the average digestibility of CP, Lys, Trp, Val, Ala or Glu between IRA modified and intact animals. Average ileal digestibilities of His, Thr, Asp, Cys, Gly, Hyp, Pro, Ser, starch and total carbohydrates (CHO) were significantly lower compared with total tract values. Average ileal digestibility of Arg, Ile, Leu, Met, Phe, Tyr and crude fat was significantly higher than total tract digestibility. Digestibility measured in IRA modified animals showed less variability compared with values from intact animals. There were significant differences among diets in ileal as well as total tract digestibility of orude protein, most amino acids, starch and CHO, and in ileal digestibility of crude fat. Ileal crude protein digestibility of the diets ranged from 81.0-86.4% and total tract digestibility from 82.5-86.4%. Ileal amino acid digestibilities ranged from 70.1 (Asp) to 93.3% (Arg) and total tract values ranged from 72.8 (Cys) to 92.2% (Arg). Both ileal and total tract digestibilities of crude protein and most amino acids were significantly lower for diets containing meat meal or bacterial protein meal compared with the control fish meal-based diet and the diet with soybean meal. Although ileal digestibility may be more accurate than total tract digestibility in estimating the protein and amino acid supply in blue foxes, total tract digestibility may be acceptable because of numerically small differences between ileal and total tract digestibilities for protein and most amino acids. It was further concluded that ileal digestibilities of starch and CHO in the blue fox are lower than corresponding total tract digestibilities.     

Healing-promoting effect of bombesin treatment on chronic gastric ulcer in rats

To evaluate whether bombesin treatment has a facilitatory effect on the healing of chronic gastric ulcer, following the induction of ulcer by serosal application of acetic acid, rats were given bombesin (30 microg/kg/day; subcutaneously) or vehicle three times a day for 7, 14 or 21 days until they were decapitated. Neither food intake nor gastric emptying rate in either vehicle-treated or bombesin-treated groups was not statistically different from control rats. Similarly, ulcer indices and gastric myeloperoxidase (MPO) activities at the first and second weeks of injury were not different among the groups. However, in the 3-week ulcer group, bombesin treatment reduced tissue MPO level significantly back to control levels. Moreover, the analysis of the surface epithelium by scanning electron and light microscopy demonstrated a significant reduction in the severity of ulcers by bombesin treatment. Pretreatment with CCK antagonists (L-364,718 or L365,260; 25 micromol/kg/day) before bombesin treatment showed that neither of the CCK antagonists had a significant effect on the bombesin-mediated healing process, suggesting that CCK receptors are not involved in the action of bombesin. In accordance with the previous studies that show its acute gastroprotective effects, bombesin is also effective in promoting the healing process of chronic gastric ulcer in rats.