Acceleration Of Gastric Emptying Research Articles

The Relation Between Symptom Improvement and Gastric Emptying in the Treatment of Diabetic and Idiopathic Gastroparesis

The relationship between symptom improvement (SI) and acceleration of gastric emptying (GE) for different drugs used in the treatment of idiopathic and diabetic gastroparesis is uncertain. In this paper we examined the study-specific correlations between SI and GE, and we performed a meta-regression analysis of the association across multiple studies. The MEDLINE database (1,946 to present) was searched, and only controlled trials or trials with an established effective comparator that compared both SI and GE were included. Studies were identified for metoclopramide (n=6), domperidone (n=6), cisapride (n=14), erythromycin (n=3), botulinum toxin (n=2), and levosulpiride (n=3). Even though most drugs concomitantly improved symptoms and accelerated GE, no study reported a significant correlation between SI and GE. Moreover, a correlation analysis over all studies using meta-regression did not show a significant relationship between SI and GE. Our findings need to be qualified by inconsistencies in study methods, which is a limitation but also suggests that our findings are robust to methodological factors. In this review, no evidence of a relationship between SI and GE was identified for different drugs used for the treatment of gastroparesis. This finding questions the use of GE measurement to direct drug development for gastroparesis.

Mo2080 First-in-Human Study of the Novel 5-HT4 Agonist, RQ-00000010, Demonstrated Acceleration of Gastric Emptying Following Single and Multiple Oral Administration to Healthy Human Subjects

Mo2080 First-in-Human Study of the Novel 5-HT4 Agonist, RQ-00000010, Demonstrated Acceleration of Gastric Emptying Following Single and Multiple Oral Administration to Healthy Human Subjects

The addition of pyloroplasty as a new surgical approach to enhance effectiveness of gastric electrical stimulation therapy in patients with gastroparesis

Improvement of gastroparesis (GP) symptoms has been documented in patients treated with gastric electrical stimulation (GES), but acceleration of gastric emptying (GET) is unpredictable. The aim of our study was to evaluate the advantage of adding surgical pyloroplasty (PP) to GES for improvement of GET and control of symptoms in diabetes mellitus (DM), idiopathic (ID), and postvagotomy (P-V) GP. A total of 49 (17 - DM, 9 - ID, 23 - P-V) consecutive GP patients: 38 female; mean age 42 (21-73 years); mean weight 158 lbs (102-245), underwent GES implantation, and 26 (53%) additionally received PP. Total Symptoms Score, 4-h GET, adverse events (AEs), and days of hospitalizations were captured at baseline and at the last visit. The mean follow-up was 7 months. Total Symptoms Score in patients who received Enterra and PP or GES alone significantly improved compared to their baseline scores (P < 0.001). GET improved by 64% at 4 h (P < 0.001) in patients with Enterra and PP, compared to 7% observed after GES therapy alone (ns). The most impressive acceleration of GET was seen in the P-V group, who received both therapies (P = 0.004) and 8 (60%) of them normalized GET. No AEs accompanied the addition of PP to the Enterra surgery. (i) In drug-refractory GP the addition of PP to GES substantially accelerated GET; (ii) The GET response in P-V group was the most impressive; (iii) Significant symptom reductions were achieved by both procedures; and (iv) PP added to GES may sustain better long-term symptoms control particularly in the P-V setting.

Role of KATP channels and TRPV1 receptors in hydrogen sulfide-enhanced gastric emptying of liquid in awake mice

Hydrogen sulphide (H2S) has shown to relax gastrointestinal muscle. Here in, we evaluated the effects of H2S donors on gastric emptying and in pyloric sphincter muscle relaxation, and whether these effects involved KATP channels or TRPV1 receptors. Mice were treated with l-cysteine (alone or with propargylglycine-an inhibitor of H2S synthesis), NaHS, Lawesson’s reagent (H2S donors) or saline. After 30min, mice were gavaged with a liquid meal containing a nonabsorbable marker and then killed at 10, 20 or 30min intervals to assess marker recovery from the stomach and intestine. This experiment was repeated in mice pre-treated with KATP channel (glibenclamide) or TRPV1 receptor (capsazepine) antagonists. In addition, pyloric sphincter muscles were mounted in an organ bath, incubated with saline, glibenclamide or capsazepine, and NaHS dose–responses were determined. H2S donors and l-cysteine enhanced gastric emptying in a dose-dependent manner; propargylglycine reversed the effect of l-cysteine. Both glibenclamide and capsazepine abolished l-cysteine and H2S donors’ augmentation of gastric emptying. Dose-dependent inductions of pyloric sphincter relaxation by NaHS were abolished by glibenclamide or capsazepine. These data suggest that H2S donors-induced acceleration of gastric emptying and relaxation of pyloric sphincter muscle by KATP channel and TRPV1 receptor activations.

Pharmacological basis for the medicinal use of muskmelon base (Pedicellus Melo.) for abdominal distention and constipation

Ethnopharmacological relevanceMuskmelon base (Pedicellus Melo.) has a long history (Ming Dynasty) as a Chinese traditional medicine. According to traditional use, it was prepared as rectal suppositories for treating abdominal distention and constipation. The present study was carried out on the pharmacological basis for the medicinal use of muskmelon base. Aim of the studyThe objective of this study was to determine the pharmacological basis for the medicinal use of the ethanol extract from muskmelon base (EMB) for abdominal distention and constipation. Materials and methodsIn this study, we report the gastrointestinal prokinetic action of EMB following single rectal or large intestinal administration. Laxative activity, gastric emptying and small intestinal transit tests were examined in ICR mice. SD rats were used to determine changes in large intestinal transit and contractile effects of the proximal colon in vivo. Guinea pigs were used to evaluate the contractile effects of the proximal colon and the possible mechanism or mechanisms on proximal colon activity ex vivo. Moreover, the acute toxicity of EMB was evaluated. ResultsIn the in vivo experiments, the acute toxicity test showed that the maximum tolerated dose (MTD) of EMB was 400mg/kg. A laxative effect was observed in mice at different dosages (6.5, 13 and 26mg/kg). EMB showed a dose-dependent acceleration of gastric emptying (13 and 26mg/kg). It also promoted both small intestinal (6.5, 13 and 26mg/kg) and large intestinal (4, 8 and 16mg/kg) transit activity. In the SD rat model, single rectal administration of EMB (8 and 16mg/kg) showed a significant increase in both the frequency and amplitude of proximal colon smooth muscle contractility. These increases in amplitude and frequency peaked 30–60min after EMB administration and corresponded with the results of the laxative activity test. The ex vivo experiments showed that varying doses of EMB (11.5, 23 and 46mg/kg) had a direct prokinetic effect that was sensitive to atropine. ConclusionsOur results show that EMB is a low dosage, fast acting drug with a large therapeutic window (4–400mg/kg) and shows significant gastrointestinal prokinetic action after single rectal or large intestinal administration. This gastrointestinal prokinetic effect was stronger in the intestines than in the stomach. This effect was sensitive to atropine, suggesting that EMB acts mainly through cholinergic mechanisms.

Accelerated Gastric Emptying but No Carbohydrate Malabsorption 1 Year After Gastric Bypass Surgery (GBP)

Following gastric bypass surgery (GBP), there is a post-prandial rise of incretin and satiety gut peptides. The mechanisms of enhanced incretin release in response to nutrients after GBP is not elucidated and may be in relation to altered nutrient transit time and/or malabsorption. Seven morbidly obese subjects (BMI = 44.5 ± 2.8kg/m(2)) were studied before and 1year after GBP with a D: -xylose test. After ingestion of 25g of D: -xylose in 200mL of non-carbonated water, blood samples were collected at frequent time intervals to determine gastric emptying (time to appearance of D: -xylose) and carbohydrate absorption using standard criteria. One year after GBP, subjects lost 45.0 ± 9.7kg and had a BMI of 27.1 ± 4.7kg/m(2). Gastric emptying was more rapid after GBP. The mean time to appearance of D: -xylose in serum decreased from 18.6 ± 6.9min prior to GBP to 7.9 ± 2.7min after GBP (p = 0.006). There was no significant difference in absorption before (serum D: -xylose concentrations = 35.6 ± 12.6mg/dL at 60min and 33.9 ± 9.1mg/dL at 180min) or 1year after GBP (serum D: -xylose = 31.5 ± 18.1mg/dL at 60min and 27.2 ± 11.9mg/dL at 180min). These data confirm the acceleration of gastric emptying for liquid and the absence of carbohydrate malabsorption 1year after GBP. Rapid gastric emptying may play a role in incretin response after GBP and the resulting improved glucose homeostasis.

Diet‐induced obesity has neuroprotective effects in murine gastric enteric nervous system: involvement of leptin and glial cell line‐derived neurotrophic factor

Nutritional factors can induce profound neuroplastic changes in the enteric nervous system (ENS), responsible for changes in gastrointestinal (GI) motility. However, long-term effects of a nutritional imbalance leading to obesity, such as Western diet (WD), upon ENS phenotype and control of GI motility remain unknown. Therefore, we investigated the effects of WD-induced obesity (DIO) on ENS phenotype and function as well as factors involved in functional plasticity. Mice were fed with normal diet (ND) or WD for 12 weeks. GI motility was assessed in vivo and ex vivo. Myenteric neurons and glia were analysed with immunohistochemical methods using antibodies against Hu, neuronal nitric oxide synthase (nNOS), Sox-10 and with calcium imaging techniques. Leptin and glial cell line-derived neurotrophic factor (GDNF) were studied using immunohistochemical, biochemical or PCR methods in mice and primary culture of ENS. DIO prevented the age-associated decrease in antral nitrergic neurons observed in ND mice. Nerve stimulation evoked a stronger neuronal Ca(2+) response in WD compared to ND mice. DIO induced an NO-dependent increase in gastric emptying and neuromuscular transmission in the antrum without any change in small intestinal transit. During WD but not ND, a time-dependent increase in leptin and GDNF occurred in the antrum. Finally, we showed that leptin increased GDNF production in the ENS and induced neuroprotective effects mediated in part by GDNF. These results demonstrate that DIO induces neuroplastic changes in the antrum leading to an NO-dependent acceleration of gastric emptying. In addition, DIO induced neuroplasticity in the ENS is likely to involve leptin and GDNF.

Effects of the Traditional Japanese Medicine Rikkunshito on Postprandial Glucose and Lipid Metabolism

Rikkunshito, a traditional Japanese medicine, has been used as a prokinetic agent to treat functional dyspepsia. Acceleration of gastric emptying of a meal may have a great impact on postprandial blood glucose and insulin responses, possibly resulting in lipid metabolism. The aim of the present study was to investigate associations between blood glucose and insulin levels and GLP-1 response after administration of solid test meals. Effects of Rikkunshito on glucose and lipid metabolism were also evaluated. A meal challenge test (cookie test) was performed on 11 healthy volunteers. Two-week intake of Rikkunshito did not affect postprandial glucose, GLP-1, triglyceride, or RLP-c responses, whereas the plasma insulin level at 60 min was significantly higher after intake of Rikkunshito. FFA levels were also lower from 60 min to 180 min after intake of Rikkunshito. This suggests that GLP-1 does not contribute to enhanced insulin secretion at 60 min after ingestion of solid test meals. It is likely that a prokinetic effect of Rikkunshito could alter insulin secretion after ingestion of solid test meals. Rikkunshito enhances insulin secretion at 60 min after taking solid meals and subsequently reduces plasma FFA levels. These may contribute to preventing metabolic syndrome.

Erratum: Meal size can be decreased in obese subjects through pharmacological acceleration of gastric emptying (The OBERYTH trial)

Erratum: Meal size can be decreased in obese subjects through pharmacological acceleration of gastric emptying (The OBERYTH trial)

The effect of Taraxacum officinale on gastric emptying and smooth muscle motility in Rodents

Taraxacum officinale (TO) is a traditional herbal medicine that has been widely used for abdominal illnesses. However, the efficacy and the mechanism of TO on gastric emptying (GE) and smooth muscle motility are unknown. Ethyl acetate fraction (EA), n-butanol fraction (BF), and aqueous fraction (AF) were prepared in succession from 70% ethanol extract (EE) of TO using solvent polarity chromatography. Phenol red meal was adopted to estimate GE in mice. A polygraph was used to measure the smooth muscle motility in rats. The percentage of GE was 48.8 ± 6.1% (vehicle control), 75.3 ± 6.5% (cisapride positive control), 68.0±6.7% (EE), 53.3±6.0% (EA), 54.1±6.3% (AF), and 86.0±6.5% (BF). Thus, BF was determined to be most effective in accelerating GE. This stimulatory effect of BF on GE was also supported by the observation that BF increased spontaneous contraction of gastric fundus and antrum and decreased the spontaneous motility of pyloric sphincter in vitro. Atropine blocked the stimulatory effect of BF on GE, whereas phentolamine and propranolol had no effect. BF seems to be a promising prokinetic agent. BF-induced increase in the contraction of fundus and antrum contributes to an increase in the intra-gastric pressure. BF-induced decrease in the motility of pyloric sphincter contributes to a decrease in the resistance of food from the stomach to the small intestine. The acceleration of GE by BF is likely to be exerted through cholinergic stimulation.

Meal size can be decreased in obese subjects through pharmacological acceleration of gastric emptying (The OBERYTH trial)

Entry of nutrients into the small intestine activates neuro-hormonal signals that regulate food intake through induction of satiation. To evaluate whether caloric intake can be decreased by pharmacologically accelerating gastric emptying (GE) of nutrients into the small intestine. Subjects were tested in 2 days, at baseline (day1) and after randomly receiving, in a double-blind manner, a 1 h infusion of erythromycin (3 mg Kg(-1), to accelerate GE) or placebo (day 2). Ad libitum caloric intake and postprandial gastrointestinal symptoms were evaluated using a validated nutrient drink test, simultaneously measuring gastric emptying [corrected] by scintigraphy. Plasma levels of satiation factors were also measured to evaluate their role in the modification of caloric intake and postprandial symptoms. Acceleration of GE was assessed as the difference in percentage emptied between day 2 and day 1 (DGE). The effects of DGE on caloric intake and symptoms were evaluated using multiple (lineal) regression. Among 30 overweight/obese subjects (24F and 6 M), 15 received erythromycin and 15 placebo. The overall median age was 36 years (IQR: 30-42) and body mass index was 30 Kg m(-2) (IQR: 27-36). Subjects receiving erythromycin on day 2 presented accelerated GE as compared with placebo (P = 0.0002). DGE at 15 min after initiating eating had a significant effect on prospective caloric intake (P = 0.004). From the best-fitted regression model (R (2) = 81%, P < 0.0001), a 10% increase in GE at 15 min induced on an average a 135 ± 43.5 Kcal decrease in caloric intake. Postprandial increase in cholecystokinin (CCK) (P = 0.03) and insulin (P = 0.02) was associated with decreased caloric intake. Acceleration of GE at 60 min after initiating eating increased postprandial symptom scores measured 30 min after the completion of food consumption (P = 0.01). Postprandial increase in CCK (P = 0.002) and PP (P = 0.02) was associated with postprandial symptoms. Meal size can be reduced in overweight/obese subjects by pharmacologically accelerating GE. This may be a reasonable target in obesity management.

Effects of Smoking Cessation on Gastric Emptying in Smokers

Smoking cessation can lead to changes in appetite and weight gain in some patients; thus, smoking cessation may alter gastrointestinal motility. Effects of smoking cessation on gastric emptying in smokers have not been established. This study sought to determine how smoking cessation affects gastric emptying in smokers. Participant group comprised 53 habitual smokers and 12 healthy nonsmokers. Habitual smokers were treated for 2 months with transdermal nicotine patches. Gastric emptying was studied using C acetate breath tests at the beginning of the study, and at 1 week and 9 weeks after cessation of patch use. Maximal CO2 excretion time (Tmax), CO2 excretion half-life (T1/2), and parameters beta and kappa, representing initial and subsequent gastric-emptying phases, respectively, were determined using conventional formulae. Before smoking cessation, Tmax was reached significantly later in smokers (0.94+/-0.3 h, P=0.014) than in controls (0.89+/-0.1 h). At 1 week after the end of treatment, Tmax was significantly decreased (from 1.05+/-0.32 h to 0.72+/-0.64 h, P=0.003). T1/2 also tended to decrease, but not significantly. Although beta was decreased significantly (from 2.46+/-0.40 to 2.17+/-0.58, P=0.022), kappa was unchanged. However, by 9 weeks after the end of treatment, Tmax (1.28+/-0.69 h) had increased to levels seen before treatment. Smoking cessation temporarily accelerates gastric emptying, and decreases in beta suggest that initial-phase gastric emptying accelerates after smoking cessation. The temporary acceleration of gastric emptying after smoking cessation may be involved in the temporary increase in appetite and weight gain seen after smoking cessation.

Clinical effects of STW 5 (Iberogast®) are not based on acceleration of gastric emptying in patients with functional dyspepsia and gastroparesis

STW 5, a herbal extract, is effective for the treatment of symptoms in patients with functional dyspepsia (FD). However, its mode of action is still unclear and a modulation of gastric motility is hypothesized. This multicentre, placebo-controlled double-blind study addressed the question of whether STW 5 accelerates gastric emptying in patients with FD and gastroparesis. One-hundred and three patients diagnosed with FD were randomly assigned to a treatment with either STW 5 or a liquid placebo for 28 days. The primary end point of the study was a change of a validated gastrointestinal symptom (GIS) score under treatment. Additionally, patients underwent a (13)C octanoic acid breath test for the assessment of the gastric half-emptying time (t(1/2)). Patients with prolonged t(1/2) were diagnosed with gastroparesis and requested to repeat the test at the end of treatment. A change of t(1/2) was defined a secondary study end point. t(1/2) was prolonged in 48.6% of patients in the STW 5 group and in 43.8% of the placebo group. During treatment, t(1/2) increased non-significantly in patients treated with STW 5 (+23 +/- 109 min; P = 0.51) and slightly accelerated among patients in the placebo arm (-26 +/- 51 min; P = 0.77) (P = 0.49). The improvement of the GIS (P = 0.08) and the proportion of patients with a treatment response (P = 0.03) were more pronounced in the STW 5 group. Our findings suggest that the clinical effects of STW 5 in patients with FD and gastroparesis are not directly mediated by an acceleration of gastric emptying. A clear-cut correlation with symptom improvement is still lacking.

Effect of spinal cord stimulation in a rodent model of post‐operative ileus

Post-operative ileus (POI) is a transient impairment of gastrointestinal (GI) transit that develops after abdominal surgery. The goal of this study was to investigate the effect of spinal cord stimulation (SCS) on gastric emptying and upper GI transit in a rat model of POI. All rats had an electrode placed on the dorsal surface of the spinal cord between the T(5) and T(8) segments. After recovery, gastric emptying and upper GI transit (geometric centre and head of meal) were assessed using a radiolabelled meal fed to each rat via oral gavage. In unanaesthetized rats, SCS (15, 25, 50, 100, 200 Hz, 0.2 ms at 90% motor threshold for 15 min) was performed immediately after the meal. The sham control group had no current applied. The naïve group was without POI or SCS. Gastric emptying was significantly delayed in sham-stimulated rats with POI compared with naïve controls (39.8 +/- 6.2%vs 76.5 +/- 4.9%, P < 0.001). In rats with POI that underwent SCS, there was a significant acceleration of gastric emptying to levels that resembled those of naïve controls (65.1 +/- 7.4%, P < 0.05). However, while SCS did not normalize the geometric centre and head of the meal when compared with the naïve group, it did significantly improve both parameters compared with the sham stimulation group. In summary, SCS normalizes gastric emptying and improves upper GI transit in a rodent model of POI. Further experiments are required to address the mechanism(s) by which SCS exhibits prokinetic activity.

Acotiamide hydrochloride (Z‐338), a novel prokinetic agent, restores delayed gastric emptying and feeding inhibition induced by restraint stress in rats

Acotiamide hydrochloride (Z-338) is a member of new class prokinetic agents currently being developed for the treatment of functional dyspepsia (FD). DNA microarray analysis showed that acotiamide altered the expressions of stress-related genes such as gamma-aminobutyric acid (GABA) receptors, GABA transporters and neuromedin U (NmU) in the medulla oblongata or hypothalamus after administration of acotiamide. Therefore, effects of acotiamide on stress-related symptoms, delayed gastric emptying and feeding inhibition, in rats were examined. Acotiamide significantly improved both delayed gastric emptying and feeding inhibition in restraint stress-induced model, but did not affect both basal gastric emptying and feeding in intact rats, indicating that acotiamide exerted effects only on gastric emptying and feeding impaired by the stress. On the other hand, mosapride showed significant acceleration of gastric emptying in intact and restraint stress-induced model, and itopride showed no effect on restraint stress-induced delayed gastric emptying. In addition, gene expression of NmU increased by restraint stress was suppressed by administration of acotiamide, while acotiamide had no effect on delayed gastric emptying induced by an intracerebroventricular administration of NmU, suggesting that the suppressive effect of acotiamide on gene expression of NmU might be important to restore delayed gastric emptying or feeding inhibition induced by restraint stress. These findings suggest that acotiamide might play an important role in regulation of stress response. As stress is considered to be a major contributing factor in the development of FD, the observed effects may be relevant for symptom improvement in FD.

Sleeve Gastrectomy—A “Food Limiting” Operation

Sleeve gastrectomy (SG), which, thus far, is showing good resolution of comorbidities and good weight loss, shows increasing popularity among bariatric surgeons. The aim of this study was to evaluate clinical outcome and the gastric emptying of solid foods, 24 months after SG. Fourteen morbidly obese patients, four males and ten females, median age 41 years (range 29-65), median body mass index (BMI) 49.46 kg/m(2) (range 41.14-55.63), who underwent SG for weight loss, were studied prospectively. Nine patients underwent gastric emptying studies, using radioisotopic technique before, 6 months and 24 months after the operation. The remaining five patients underwent gastric emptying studies, 6 months and 24 months after the operation. A significant reduction in patients' weight and BMI was evident at 6, 12 and 24 months postoperatively. In the nine patients who underwent gastric emptying studies pre-, 6 and 24 months postoperatively, the T-lag phase duration significantly decreased, following the SG, from 17.30 (range 15.50-20.90) min, to 12.50 (range 9.20-18.00) min at 6 months and 12.16 (range 10.90-20.00) min at 24 months postoperatively (P < 0.05). The gastric emptying half time (T1/2) accelerated significantly postoperatively from 86.50 (range 77.50-104.60) min, to 62.50 (range 46.30-80.00) min at 6 months and 60.80 (range 54.80-100.00) min at 24 months after SG (P < 0.05). The percentage of gastric emptying (%GE) increased significantly postoperatively, from 52 (range 43-58) % to 72 (range 57-97) % at 6 months and 74 (range 45-82) % at 24 months, following SG (P < 0.05). No differences in gastric emptying were observed, when values at 24 months were compared to those at 6 months postoperatively. When the whole group of 14 patients was studied, there were also no significant changes in T-lag, T1/2 and %GE between 6 and 24 months postoperatively. Our study indicates the constant effect of SG in the acceleration of gastric emptying of solids, which occurs faster, not only in short but also in long-term postoperatively. Such effects on gastric motility, in combination with the reported alterations in gut hormones, may explain how this 'food limiting' operation results in weight loss.

Role of Ghrelin in the Relationship Between Hyperphagia and Accelerated Gastric Emptying in Diabetic Mice

Ghrelin is an orexigenic peptide with gastroprokinetic effects. Mice with streptozotocin (STZ)-induced diabetes exhibit hyperphagia, altered gastric emptying, and increased plasma ghrelin levels. We investigated the causative role of ghrelin herein by comparing changes in ghrelin receptor knockout (growth hormone secretagogue receptor [GHS-R](-/-)) and wild-type (GHS-R(+/+)) mice with STZ-induced diabetes. Gastric emptying was measured with the [(13)C]octanoic acid breath test. The messenger RNA (mRNA) expression of neuropeptide Y (NPY), agouti-related peptide (AgRP), and proopiomelanocortin was quantified by real-time reverse-transcription polymerase chain reaction. Neural contractions were elicited by electrical field stimulation in fundic smooth muscle strips. Diabetes increased plasma ghrelin levels to a similar extent in both genotypes. Hyperphagia was more pronounced in GHS-R(+/+) than in GHS-R(-/-) mice between days 12 and 21. Increases in NPY and AgRP mRNA expression were less pronounced in diabetic GHS-R(-/-) than in GHS-R(+/+) mice from day 15 on, whereas decreases in proopiomelanocortin mRNA levels were similar in both genotypes. Gastric emptying was accelerated to a similar extent in both genotypes, starting on day 16. In fundic smooth muscle strips of diabetic GHS-R(+/+) and GHS-R(-/-) mice, neuronal relaxations were reduced, whereas contractions were increased; this increase was related to an increased affinity of muscarinic and tachykinergic receptors. Diabetic hyperphagia is regulated by central mechanisms in which the ghrelin-signaling pathway affects the expression of NPY and AgRP in the hypothalamus. The acceleration of gastric emptying, which is not affected by ghrelin signaling, is not the cause of diabetic hyperphagia and probably involves local contractility changes in the fundus.

S1853 Eating Behavior Modulates Ghrelin Surge, Resulting in Potent Interdigestive Gastric Contractions and Acceleration of Gastric Emptying in Rats

S1853 Eating Behavior Modulates Ghrelin Surge, Resulting in Potent Interdigestive Gastric Contractions and Acceleration of Gastric Emptying in Rats

Effect of chronic stress on gastric emptying and plasma ghrelin levels in rats

Chronic stress is associated with gastrointestinal functional diseases. Although the pathophysiology seems to be associated with gastrointestinal motility, their mechanisms remain unclear. We investigated gastric emptying and chemical mediators under conditions of continuous stress, which were produced using 8-week-old male Wistar rats kept in a cage filled with water to 2 cm height for 5 days. We examined gastric emptying by the phenol red method and chemical mediators at 4, 8, and 24 h and 3 and 5 days after initiation of stress restraint. Plasma ACTH level was significantly higher in the stress throughout the period of measurement. Continuous stress delayed gastric emptying until 24 h: peak delay was observed at 8 h, whereas gastric emptying was accelerated on days 3 and 5. Plasma noradrenalin level was significantly elevated at every time point until 24 h. Guanethidine pretreatment eliminated the delay in gastric emptying at 8 h. Active ghrelin was significantly increased on days 3 and 5 after peak (at 24 h) plasma total and desacyl ghrelin in the stress group. Number of ghrelin-immunoreactive cells and level of preproghrelin mRNA expression in the gastric body increased in parallel with plasma active ghrelin level. Pretreatment with growth hormone secretagogue receptor antagonist at 5 days partially inhibited the stress-induced acceleration of gastric emptying. Delayed gastric emptying at acute phase of continuous stress was mediated via sympathetic pathway, while acceleration at chronic phase was mediated via increased active ghrelin release from the stomach.

Fixed feeding potentiates interdigestive gastric motor activity in rats: importance of eating habits for maintaining interdigestive MMC

Endogenous ghrelin regulates the occurrence of interdigestive gastric phase III-like contractions in rats. However, the fasted motor pattern is not as regular and potent in humans and dogs. We hypothesize that eating habits play an important role in maintaining a regular interdigestive gastric contractions. We studied the effect of fixed-feeding regimen on interdigestive gastric contractions and plasma acyl ghrelin levels. The fixed-fed rats were trained to the assigned meal feeding regimen, once daily at 12:00 PM to 4:00 PM for 14 days. Free-fed rats were maintained with free access to food. As ghrelin regulates gastric emptying as well, solid gastric emptying was also studied in fixed-fed rats and free-fed rats. In free-fed rats, two of six rats did not show interdigestive gastric phase III-like contractions. In contrast, phase III-like contractions were observed in all rats 14 days after starting the fixed-feeding regimen. The maximal amplitude of phase III-like contractions significantly increased from 8.4 +/- 0.6 to 16.3 +/- 1.8 g (n = 6, P < 0.05) 14 days after the start of the fixed feeding. Fasted and postprandial plasma ghrelin levels were significantly increased after 14 days of fixed feeding. Solid gastric emptying was significantly accelerated in fixed-fed rats (72.1 +/- 4.2%) compared with that of free-fed rats (58.7 +/- 2.7%, n = 6, P < 0.05). Our present findings suggest that fixed feeding increases plasma ghrelin levels, potent interdigestive contractions, and acceleration of gastric emptying.