Decrease In Gastric Emptying Research Articles

Effect of anaerobic resistance training on gastric emptying of solids, nutritional parameters and food behavior in the rats treated with dexamethasone

Dexamethasone (Dexa) is a potent glucocorticoid that can trigger side effects, such as neuromuscular, cardiovascular, and gastric motility disorders. Exercise can ameliorate gastrointestinal disorders. However, it is not clear whether exercise can modulate the side effects of using Dexa on gastric motility. To investigate the role of anaerobic resistance training (ART) on gastric motility and feeding behavior of rats treated with dexamethasone, rats were divided into three groups: control (Ctrl), dexamethasone (Dexa), and anaerobic resistance training + dexamethasone (ARTDexa). Anaerobic resistance training (ART) consisted of climbing a vertical ladder 5 days/week (with intensity of 50% to 100% of the maximum overload/8 weeks). At the end of the ART or control period, the rats received Dexa (1 mg/kg i.p) for 10 consecutive days. In the end, we evaluated anthropometric parameters and feeding behavior, heart rate, gastric emptying, and lipid profile in all groups. We observed significant decrease (p < 0.05) in body weight and food intake in the Dexa and ARTDexa groups compared to the control. Dexa promoted significant tachycardia (p < 0.05) and a decrease (p < 0.05) in the r-r’ interval. The ART significantly prevented (p < 0.05) cardiovascular effects. Dexa induced a decrease (p < 0.05) in gastric emptying compared to the control group. On the other hand, ART significantly prevented (p < 0.05) the decrease in gastric emptying compared to Dexa. The chronic use of Dexa caused tachycardia, decreased food intake, and decreased gastric emptying. The ART modulated cardiovascular parameters, improving tachycardia. In addition, this exercise prevented gastric dysmotility induced by dexamethasone.

The Effect of the Intra-gastric Balloon on Gastric Emptying and the DeMeester Score.

The mechanism of weight loss with the intra-gastric balloon (IGB) is thought to be a decrease in gastric emptying (GE); however the evidence is conflicting. Nausea, abdominal pain, and gastroesophageal reflux disease (GERD) can cause intolerance resulting in early removal. This is demoralizing for the patient and costly for the healthcare system. The ability to predict which patients will have superior weight loss and tolerance is invaluable. We sought to investigate if the IGB induced weight loss by reducing GE and the effect of the IGB on the DeMeester score. We retrospectively reviewed prospectively collected data for patients undergoing IGB placement at a single hospital. Manometry and pH studies were performed before and with the IGB in place. Weight was measured at baseline, at removal, and 6months later. Adverse events leading to early removal were recorded. Twenty-four patients were evaluated. There was a statistically significant decrease in GE for solids with the IGB (117.92 ± 150.23 vs 281.48 ± 206.49min; p = 0.0048), but not for liquids (54.44 ± 17.97 vs 56.08 ± 43.96min; p = 0.7228). The lower esophageal sphincter (LES) pressure did not change significantly with placement of the IGB (17.76 ± 7.39 vs 14.74 ± 7.24mmHg; p = 0.09). On multivariate analysis, increase in DeMeester score was associated with total body weight loss (p = 0.0125) and change in GE (p = 0.038) independently. The IGB delays GE for solids, but not for liquids, and increases the DeMeester score by a mechanism other than a loss of LES pressure.

Effect of pirfenidone on gastric emptying in a rat model

IntroductionGastrointestinal (GI) adverse events (AEs) are commonly reported in patients with idiopathic pulmonary fibrosis who are treated with pirfenidone. Taking pirfenidone with a substantial amount of food or dividing the dose over the course of a meal has been reported to reduce the frequency of GI AEs in clinical practice. In humans, the maximum plasma concentration (Cmax) of pirfenidone was reduced when the drug was taken with food compared with the fasting state, and the lower Cmax was associated with a reduction in GI AE rates. In this study, the effects of the divided-dose approach and timing of pirfenidone administration relative to meal intake on gastric emptying were assessed using a rat model. The aim of this study was to investigate whether modification of dosing regimens could minimize pirfenidone's effect on inhibition of gastric emptying. MethodsGastric emptying was assessed in male Sprague-Dawley rats after administration of a test meal by weighing stomach contents at various time points up to 120 min after the meal. Pirfenidone was administered via oral gavage either as a single-bolus dose of 30 mg/kg or as divided doses of 3 × 10 mg/kg at intervals ranging from 10 to 30 min for a total duration of 30 to 90 min. In addition, the test meal was given either at 30 min before, coincident with, or 30 min following pirfenidone oral administration. ResultsAdministration of an oral 30-mg/kg single-bolus dose of pirfenidone with a meal resulted in a statistically significant decrease in gastric emptying in a rat model. The effect of pirfenidone on decreasing gastric emptying was lessened when the same total dose (i.e., 30 mg/kg) was administered as 3 divided doses (i.e., 3 × 10 mg/kg) over intervals up to 30 min in between each divided dose. Pharmacokinetic simulation suggested that a divided-dosing regimen would decrease pirfenidone Cmax relative to single-bolus administration. When the same single-bolus dose of 30 mg/kg was administered 30 min following a meal rather than coincident with a meal, pirfenidone's effect on decreasing gastric emptying was reduced to the same extent as when the dose was divided as 3 × 10 mg/kg over a 90-min period. ConclusionsAdministration of pirfenidone 30 min after a meal as a single-bolus dose or a divided dose over a 90-min period blunted pirfenidone's effect on inhibition of gastric emptying in rats compared with pirfenidone administration as a single-bolus dose coincident with a meal. Decreased gastric emptying, which is associated with pirfenidone administration, may be one of the contributing factors leading to GI tolerability issues associated with pirfenidone use in humans. Modification of the dosing regimen diminished this impact and may provide insight into possible mitigation strategies to minimize GI-related toxicities in the clinic.

Diabetes-induced oxidative stress mediates upregulation of RhoA/Rho kinase pathway and hypercontractility of gastric smooth muscle.

The pathogenesis of diabetes-associated motility disorders are multifactorial and attributed to abnormalities in extrinsic and intrinsic innervation, and a decrease in the number of interstitial cells of Cajal, and nNOS expression and activity. Here we studied the effect of hyperglycemia on smooth muscle function. Using smooth muscles from the fundus of ob/ob mice and of wild type (WT) mice treated with 30 mM glucose (HG), we identified the molecular mechanism by which hyperglycemia upregulates RhoA/Rho kinase pathway and muscle contraction. RhoA expression, Rho kinase activity and muscle contraction were increased, while miR-133a expression was decreased in smooth muscle of ob/ob mice and in smooth muscle treated with HG. Intraperitoneal injections of pre-miR-133a decreased RhoA expression in WT mice and reversed the increase in RhoA expression in ob/ob mice. Intraperitoneal injections of antagomiR-133a increased RhoA expression in WT mice and augmented the increase in RhoA expression in ob/ob mice. The effect of pre-miR-133a or antagomiR-133a in vitro in smooth muscle treated with HG was similar to that obtained in vivo, suggesting that the expression of RhoA is negatively regulated by miR-133a and a decrease in miR-133a expression in diabetes causes an increase in RhoA expression. Oxidative stress (levels of reactive oxygen species and hydrogen peroxide, and expression of superoxide dismutase 1 and NADPH oxidase 4) was increased in smooth muscle of ob/ob mice and in HG-treated smooth muscle. Treatment of ob/ob mice with N-acetylcysteine (NAC) in vivo or addition of NAC in vitro to HG-treated smooth muscle reversed the effect of glucose on the expression of miR-133a and RhoA, Rho kinase activity and muscle contraction. NAC treatment also reversed the decrease in gastric emptying in ob/ob mice. We conclude that oxidative stress in diabetes causes a decrease in miR-133a expression leading to an increase in RhoA/Rho kinase pathway and muscle contraction.

The Effect of Gastrostomy Placement on Gastric Function in Children: a Prospective Cohort Study

BackgroundA gastrostomy placement is frequently performed in pediatric patients who require long-term enteral tube feeding. Unfortunately, postoperative complications such as leakage, feeding intolerance, and gastroesophageal reflux frequently occur. These complications may be due to postoperative gastric dysmotility. Our aim was to evaluate the effect of gastrostomy placement on gastric emptying in children. MethodsA prospective study was performed including 50 children undergoing laparoscopic gastrostomy. Before and 3 months after gastrostomy, assessment was performed using the 13C-octanoic acid breath test, 24-h pH monitoring, and reflux symptom questionnaires. ResultsGastric half-emptying time significantly increased from the 57th to the 79th percentile (p < 0.001) after gastrostomy (p < 0.001). Fifty percent of patients with normal preoperative gastric emptying develop delayed gastric emptying (DGE, P > 95) after gastrostomy (p = 0.01). Most patients (≥75%) with leakage and/or feeding intolerance after gastrostomy had DGE after operation. A decrease in gastric emptying was associated with an increase in esophageal acid exposure time (r = 0.375, p < 0.001). ConclusionGastrostomy placement in children causes a significant delay in gastric emptying. Postoperative DGE was associated with gastroesophageal reflux and was found in most patients with postoperative leakage and feeding intolerance. These negative physiologic effects should be taken into account when considering gastrostomy placement in children.

Impaired Interoception in a Preclinical Model of Functional Dyspepsia

IntroductionThe etiologies of functional dyspepsia symptoms, including postprandial distress syndrome, remain unknown. We tested the hypothesis that neonatal colon inflammation induces postprandial distress syndrome-like symptoms in adult life that associate with increased activation of vagal afferent pathways and forebrain limbic regions.ResultsThese rats showed a significant decrease in nutrient meal consumption to satiety after an overnight fast, decrease in gastric emptying, decrease in total distance traveled, and decrease in percent distance traveled in midfield versus control rats in open field test, indicating postprandial anxiety- and depression-like behaviors. Adult naïve rats treated with oral iodoacetamide to induce H. pylori-like mild gastritis demonstrated similar postprandial effects as the above rats.ConclusionsWe concluded that neonatal colon inflammation is a risk factor for the development of postprandial distress syndrome-like symptoms. While mild gastritis can induce symptoms similar to those of neonatal colon inflammation, gastritis in these rats does not worsen the symptoms.

Neuromedin U inhibits food intake partly by inhibiting gastric emptying

Neuromedin U (NMU) is a gut-brain peptide, implicated in energy and glucose homeostasis via the peripherally expressed NMU receptor 1 (NMUR1) and the central NMUR2. We investigated the effects of a lipidated NMU analog on gastric emptying (GE), glucose homeostasis and food intake to evaluate the use of a NMU analog as drug candidate for treatment of obesity and diabetes. Finally mRNA expression of NMU and NMUR1 in the gut and NMUR2 in the hypothalamus was investigated using a novel chromogen-based in situ hybridization (ISH) assay. Effects on food intake (6 and 18h post dosing) were addressed in both mice and rats. The effects on GE and glycaemic control were assessed in mice, immediately after the first dose and after seven days of bidaily (BID) dosing. The lipidated NMU analog exerted robust reductions in GE and food intake in mice and improved glycaemic control when measured immediately after the first dose. No effects were observed after seven days BID. In rats, the analog induced only a minor effect on food intake. NMU mRNA was detected in the enteric nervous system throughout the gut, whereas NMUR1 was confined to the lamina propria. NMUR2 was detected in the paraventricular (PVN) and arcuate nuclei (ARC) in mice, with a reduced expression in ARC in rats. In summary, the anorectic effect of the lipidated NMU is partly mediated by a decrease in gastric emptying which is subject to tachyphylaxis after continuous dosing. Susceptibility to NMU appears to be species specific.

Effects of sea buckthorn (Hippophaë rhamnoides L.) pulp oils on the gastric secretion, gastric emptying and its analgesic activity

Sea buckthorn (Hippophae rhamnoides L.) pulp oils (SBPO) were evaluated for its effect on gastric secretory function, gastric emptying and analgesic activity, as a potential treatment for stomach discomfort and gastric ulcers. The actions of SBPO on gastric acid, pepsin and mucus secretions were studied in Shay rats. SBPO, when administered for 7 days at the dose of 3.5 and 7.0 ml/kg, caused a significant decrease in gastric volume, total acidity and pepsin output. There was also a significant increase in gastric mucus production. Gastric emptying was studied using a carboxymethyl cellulose solution as a non-nutrient meal in mice. SBPO caused a significant decrease in gastric emptying. The antinociceptive effect was evaluated using the acetic acid induced writhing test. SBPO significantly inhibited the number of writhing responses. These results suggest effectiveness of SBPO in stomach discomfort and gastric ulcers. Key words: Hippophae rhamnoides, Sea buckthorn pulp oil, gastric secretion, gastric emptying, antinociceptive effect.

Impaired ghrelin signaling is associated with gastrointestinal dysmotility in rats with gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) is often associated with decreased upper gastrointestinal motility, and ghrelin is an appetite-stimulating hormone known to increase gastrointestinal motility. We investigated whether ghrelin signaling is impaired in rats with GERD and studied its involvement in upper gastrointestinal motility. GERD was induced surgically in Wistar rats. Rats were injected intravenously with ghrelin (3 nmol/rat), after which gastric emptying, food intake, gastroduodenal motility, and growth hormone (GH) release were investigated. Furthermore, plasma ghrelin levels and the expression of ghrelin-related genes in the stomach and hypothalamus were examined. In addition, we administered ghrelin to GERD rats treated with rikkunshito, a Kampo medicine, and examined its effects on gastroduodenal motility. GERD rats showed a considerable decrease in gastric emptying, food intake, and antral motility. Ghrelin administration significantly increased gastric emptying, food intake, and antral and duodenal motility in sham-operated rats, but not in GERD rats. The effect of ghrelin on GH release was also attenuated in GERD rats, which had significantly increased plasma ghrelin levels and expression of orexigenic neuropeptide Y/agouti-related peptide mRNA in the hypothalamus. The number of ghrelin-positive cells in the gastric body decreased in GERD rats, but the expression of gastric preproghrelin and GH secretagogue receptor mRNA was not affected. However, when ghrelin was exogenously administered to GERD rats treated with rikkunshito, a significant increase in antral motility was observed. These results suggest that gastrointestinal dysmotility is associated with impaired ghrelin signaling in GERD rats and that rikkunshito restores gastrointestinal motility by improving the ghrelin response.

Loss of intramuscular and submuscular interstitial cells of Cajal and associated enteric nerves is related to decreased gastric emptying in streptozotocin‐induced diabetes

Interstitial cells of Cajal (ICC) are associated with afferent innervation and peristalsis of the stomach suggestive of a key role in the pathophysiology of gastroparesis. We studied changes in the density and ultrastructure of ICC and enteric nerves in the streptozotocin-induced diabetes mellitus (STZ-DM) in Wistar rats using immunohistochemistry and electron microscopy. Gastric emptying was studied in vivo by single-photon emission computed tomography. In the STZ-DM antrum, a marked reduction was observed in the density of the intramuscular ICC (ICC-IM) and ICC located at the submucosal border of the circular muscle layer of the antrum (ICC-SM). The surviving ICC showed lamellar bodies and partial vacuolation of the cytoplasm content, loss of connections between ICC-IM and nerves; it appeared that injured ICC-IM developed into fibroblast-like ICC. ICC associated with Auerbach's plexus (ICC-AP) in the antrum and ICC in the fundus were not affected significantly except for a loss of connections with nerve structures. Marked reduction in nerve tissue (Protein Gene Product-9.5 positivity) was also restricted to the muscle layers including nitrergic nerves (neuronal nitric oxide synthase positivity). In vivo assessed gastric emptying was markedly reduced in STZ-DM rats. Our data demonstrate in the STZ-DM rat stomach a decreased density of ICC limited to the antrum and to ICC-IM and ICC-SM, and structural degeneration in ICC-IM and associated nerves with a special emphasis on loss of synaptic connections, accompanied by a decrease in gastric emptying. Hence, in this model of gastroparetic diabetes, regional injury to subsets of ICC and nerves are associated with gastric motor dysfunction.

Effect of cannabidiol on sepsis‐induced motility disturbances in mice: involvement of CB1 receptors and fatty acid amide hydrolase

Sepsis is an inflammatory condition that is associated with reduced propulsive gastrointestinal motility (ileus). A therapeutic option to treat sepsis is to promote intestinal propulsion preventing bacterial stasis, overgrowth and translocation. Recent evidence suggests that anti-oxidants improve sepsis-induced ileus. Cannabidiol, a non-psychotropic component of Cannabis sativa, exerts strong anti-oxidant and anti-inflammatory effects without binding to cannabinoid CB(1) or CB(2) receptors. Cannabidiol also regulates the activity of fatty acid amide hydrolase (FAAH) which is the main enzyme involved in endocannabinoid breakdown and which modulates gastrointestinal motility. Because of the therapeutic potential of cannabidiol in several pathologies, we investigated its effect on sepsis-induced ileus and on cannabinoid receptor and FAAH expression in the mouse intestine. Sepsis was induced by treating mice with lipopolysaccharides for 18 h. Sepsis led to a decrease in gastric emptying and intestinal transit. Cannabidiol further reduced gastrointestinal motility in septic mice but did not affect gastrointestinal motility in control mice. A low concentration of the CB(1) antagonist AM251 did not affect gastrointestinal motility in control mice but reversed the effect of cannabidiol in septic mice. Sepsis was associated with a selective upregulation of intestinal CB(1) receptors without affecting CB(2) receptor expression and with increased FAAH expression. The increase in FAAH expression was completely reversed by cannabidiol but not affected by AM251. Our results show that sepsis leads to an imbalance of the endocannabinoid system in the mouse intestine. Despite its proven anti-oxidant and anti-inflammatory properties, cannabidiol may be of limited use for the treatment of sepsis-induced ileus.

Effect of sodium fluoride on gastric emptying and intestinal transit in mice

Fluoride, a well-recognised harmful substance, is easily absorbed by the gastrointestinal mucosa. It is therefore conceivable that any alteration of the gastrointestinal motility can affect the rate of absorption of fluoride and leads to aggravation of its toxic effects. The effects of fluoride on gastric emptying and intestinal transit were studied in the mouse using a carboxymethyl cellulose (CMC) solution as a non-nutrient meal. The participation of the cholinergic and nitrergic systems in these effects was also evaluated. Oral gavage of 5 mM NaF had no significant effect on gastric emptying and intestinal transit of the CMC meal, whereas a decrease of gastric emptying (−33%, P < 0.05 ) and an increase in intestinal transit (+20.7%, P < 0.05 ) were observed with 20 mM NaF. Atropine injection induced a significant decrease of gastric emptying. Combined treatment of atropine with 20 mM NaF brought about a further, but not significant decrease in gastric emptying. N-G-nitro- l-arginine-methyl ester (L-NAME) treatment with or without oral administration of NaF decreased gastric emptying. Atropine treatment significantly depressed intestinal transit from 56.5% to 37.7% in the absence of NaF and from 70.1% to 42.8% in its presence. In contrast, L-NAME administration either alone or with fluoride increased intestinal transit ( P < 0.05 ). The present results suggest that fluoride alter gastrointestinal motility, an effect that may partly involve the cholinergic pathway.

The effect of bacterial lipopolysaccharide on the gastric emptying of rats: a pretreatment evaluation using dexamethasone and methylene blue

The nitric oxide might be a putative mediator of the decrease in gastric emptying induced by bacterial lipopolysaccharide in rats. For that, we evaluated the effect of the pretreatment intravenous with dexamethasone and methylene blue in the retardation process of gastric emptying induced by intravenous application of lipopolysaccharide in rats. Dexamethasone has been shown to inhibit the induction of NOS II (induced NO-synthase) while the methylene blue, that blocks the soluble guanylyl cyclase, inhibits nitric oxide synthases and, in addition, inactivates nitric oxide directly. Male Wistar rats, specific patogenic free, were used after a 24 hour fast and 1 hour-water withdrawn. The pretreatment was performed using dexamethasone solutions (3 and 6 mg/kg), methylene blue (2 mg/kg) or sterile vehicle. The treatment consisted in the application of lipopolysaccharide (50 mug/kg) or vehicle. The time period between the pretreatment and treatment was 10 minutes, excluding the study with dexamethasone 6 mg/kg that was 1 hour. The gastric emptying was evaluated 1 hour after the lipopolysaccharide application, except for two studies with dexamethasone 3 mg/kg in which the time periods were 2 and 8 hours. A saline solution containing phenol red was used as the test meal. The gastric emptying was determined by measuring gastric retention 10 minutes after the orogastric infusion of the test meal. The pretreatment with dexamethasone or methylene blue and treatment with vehicle did not have effect in the gastric emptying comparing to the control group. We found that pretreatment with dexamethasone in the studies for 1 hour and 2 hours did not interfere in the retardation of the gastric emptying produced by endotoxin. Nevertheless, in the eighth period study with this drug there was a significant reduction of gastric retention in the endotoxin-treated animals in relation to the unpretreated ones. Meanwhile, the pretreatment with the methylene blue completely blocked the action of endotoxin on the gastric emptying in rats. These results suggest a possible involvement of nitric oxide on the effect of lipopolysaccharide in rat gastric emptying.

Effects of gastroprokinetic agents on gastroparesis in streptozotocin-induced diabetic rats.

The influence of diabetic hyperglycemia on solid gastric emptying in rats was examined. Diabetes was produced by streptozotocin (STZ, 40 mg/kg i.v.), and diabetic hyperglycemia was observed from 1 day after the STZ injection. The gastric emptying of glass beads in the diabetic rats was significantly delayed compared with that in age-matched control rats at 1, 3 and 7 days after diabetes induction. A slight decrease in gastric emptying was observed in the diabetic rats from 2 to 52 weeks after the diabetes induction. We also investigated the influence of gastroprokinetic agents on STZ-induced diabetic gastroparesis and subdiaphragmatic vagotomy-induced gastroparesis in rats. The selective 5-HT3 receptor antagonists ramosetron (YM060), YM114 (KAE-393), granisetron and ondansetron, and the substituted benzamides (5-HT4 receptor agonist/5-HT3 receptor antagonists) cisapride mosapride and SC-53116 dose-dependently enhanced gastric emptying in normal rats. These compounds also reversed the impairment of diabetic gastroparesis rats at 7 days after the STZ injection, but higher doses were required. The solid gastric emptying in subdiaphragmatic vagotomized rats was also delayed. Ramosetron and the substituted benzamides cisapride and zacopride partially reversed the gastroparesis in the vagotomized rats. These results suggest that acute hyperglycemia is important mechanism for the delay of solid gastric emptying in diabetic rats. It is also suggested that selective 5-HT3 receptor antagonists and substituted benzamides enhance gastric emptying not only in normal rats but also in diabetic and vagotomized rats.

Amylin given by central or peripheral routes decreases gastric emptying and intestinal transit in the rat.

The effect of rat amylin on gastric emptying and intestinal transit in the rat was examined. Amylin administered intracerebroventricularly (1, 2, 2.5 or 4 micrograms/rat) produced the maximal decrease in gastric emptying and intestinal transit at the dose of 2.5 micrograms/rat. Higher doses produced a lower effect. Peripheral administration (25, 50 or 100 micrograms/kg) produced dose-dependent effects. Pre-treatment with neostigmine blocked the effect of amylin when it was centrally injected, while the effect of amylin given peripherally was partially reduced. Pre-treatment with domperidone decreased the inhibitory effect of peripherally injected amylin, but no effect was observed when the peptide was centrally injected.

Strenuous exercise decreases motility and cross-sectional area of human gastric antrum

Gastric emptying in humans is delayed with strenuous exercise. We used ultrasound imaging in six healthy volunteers to determine whether changes in motility and configuration of the gastric outlet contribute to this delay. After fasting, all individuals ingested chicken broth and garbanzo beans. With subjects sitting upright, transverse and longitudinal real-time views of the gastric antrum were recorded on video tape. In the exercise studies, subjects pedaled an ergometer for 10 min to attain a heart rate of 85% predicted maximum. On a different day, all subjects had an identical study without exercise. The order of performance of exercise and no-exercise studies was randomized. After exercise, contraction frequencies and antral areas were significantly reduced compared to the studies without exercise. In addition, after exercise there was closure of the pylorus and tubular narrowing of the gastric antrum. Closure of the pylorus and decreased gastric antral area and motility may be important in explaining the decrease in gastric emptying that occurs with strenuous exercise.

Hypergastrinemia is associated with decreased gastric acid secretion in 2,3,7,8-tetrachlorodibenzo- p-dioxin-treated rats

2,3,7,8-Tetrachlorodibenzo- p-dioxin (TCDD) produces a delayed onset hypergastrinemia in rats. The purpose of the present study was to determine if the increased serum gastrin concentrations were caused by decreased gastric acid secretion, decreased plasma clearance of gastrin, and/or decreased gastric emptying. It was found that TCDD treatment decreased gastric acid secretion as determined by decreases in gastric secretory volume, acidity, and total acid output in pylorus-ligated rats. Also, both dose-response and time-course curves for decreased gastric acid secretion in TCDD-treated rats were similar to those for hypergastrinemia. These findings, as well as a significant inverse correlation between serum gastrin concentrations and total gastric acid output in rats treated with graded doses of TCDD (5–100 μg/kg), suggest that TCDD-induced decreases in gastric acid production cause elevated serum gastrin concentrations. Neither hypergastrinemia nor decreased gastric acid secretion were observed in pair-fed control rats, demonstrating that neither effect was secondary to undernutrition. The TCDD-induced decrease in gastric acid secretion was not caused by a decrease in the number of acid-secreting parietal cells in the stomach, but rather was associated with a decrease in parietal cell responsiveness to gastrin-elicited acid secretion. This was evidenced by both elevated serum gastrin concentrations and a pharmacological dose of pentagastrin failing to stimulate gastric acid secretion in TCDD-treated rats. The disappearance of iv-administered gastrin-17 from the serum was not affected by TCDD treatment, suggesting that reduced serum gastrin clearance is not responsible for the TCDD-induced hypergastrinemia. Although a marked decrease in gastric emptying of a 51Cr-labeled liquid test meal was also observed in TCDD-treated rats, the lowest dose of TCDD required to produce this effect was greater than that needed to cause hypergastrinemia. This suggests that the hypergastrinemic effect of TCDD is not secondary to a decrease in gastric emptying. We conclude that the most probable cause of hypergastrinemia in TCDD-treated rats is decreased gastric acid secretion.

Aspirin-induced changes in gastric function: Role of endogenous prostaglandins and mucosal damage

The relative roles of prostaglandins and mucosal injury in aspirin-induced changes in gastric function were evaluated. Conscious rhesus monkeys received a subcutaneous injection of sodium bicarbonate or aspirin (25, 50, 100, or 150 mg/kg) and sodium bicarbonate or 150 mg/kg aspirin subcutaneously plus oral sucralfate (25 mg/kg twice a day). Gastric emptying and fluid and H+ outputs were determined during a fasting period and after an 80-ml water load using a 99mTc-diethyIenetriaminepentaacetic acid dilution technique. At the end of each study, the monkeys were gastroscoped to assess mucosal damage, which was ranked blindly on a scale of 0 to 5. Biopsy samples were taken from antrum and fundus for determination of prostaglandins and histological evaluation. All doses of aspirin significantly suppressed prostaglandins in both the antrum and fundus. In contrast, the aspirin-induced increase in gastric mucosal injury was dose dependent. Aspirin also produced a dose-dependent decrease in gastric emptying that was significantly correlated with erosions scores. When aspirin-induced lesions were prevented by sucralfate, the inhibition of gastric emptying was blocked during the fasting period and was attenuated following the water load. Acid secretion was also decreased significantly by aspirin. This action was not modified by sucralfate protection, suggesting that aspirin has a direct inhibitory effect on parietal cell secretion. These data show that mucosal damage contributes significantly to the aspirin-induced changes in gastric function. Moreover, prostaglandins may play a role in the control of gastric emptying, especially during early phase of the response to a water load.

Effects of cholecystokinin, secretin, and pancreatic polypeptide on secretion of gastric inhibitory polypeptide, insulin, and glucagon

Although the capacity of food components to cause more insulin secretion when given orally than when given intravenously is related significantly to increased plasma concentration of gastric inhibitory polypeptide (GIP), stimulated only by the oral route, questions arise as to what extent other gastrointestinal hormones modify insulin secretion either directly or by influencing the secretion of GIP. The triacontatriapeptide form of cholecystokinin (CCK 33), infused in dose gradients intravenously in dogs increases insulin secretion, and comparably to equimolar doses of the carboxy-terminal octapeptide of cholecystokin (CCK 8); neither compound changes fasting plasma levels of GIP or glucose. Glucagon was increased only by the largest dose of CCK 8 (0.27 ug/kg). Unlike the situation with GIP, it is not necessary to increase the plasma glucose above fasting level to obtain the insulin-releasing action of CCK. When glucose is infused intravenously (2 g in 0.5 min) at the beginning of a 15-minute infusion of CCK 8 (10 ng/kg/min), the amount of insulin release is greater than is produced by CCK 8 or glucose alone. In the same type of experiment, the infusion of GIP, in equimolar amounts as CCK 8, plus glucose causes no more insulin secretion than is stimulated by glucose alone. Secretin has only a small stimulating action on insulin release, and pancreatic polypeptide (PP) has no effect. Neither secretin nor PP affects GIP secretion, whether either is given alone, or together, or with CCK 8. Either secretin or CCK 8 inhibits oral glucose-stimulated increase in plasma GIP. These inhibitory effects are probably very much related to the hormone-induced decrease in gastric emptying, but changes in somatostatin secretion and other hormones possibly exert contributory actions. In conclusion, GIP in certain dose ranges has been reported to cause major increase in insulin secretion, but we showed that the insulin-releasing action of a small dose of glucose (2 g) infused intravenously was not augmented by GIP (44.5 ng/kg/min), although it was significantly increased by an equimolar dose of CCK 8. When plasma glucose was maintained at a fasting level, gradient equimolar dosages of CCK 8 and CCK 33 had comparable insulin-releasing action; GIP had no effect.

Gastric emptying of lactose and milk in subjects with lactose malabsorption.

Six lactose absorbers (LA) and 5 lactose malabsorbers (LM) had tests of gastric emptying with 750-ml meals of glucose in water, lactose in water, plain milk, and chocolate milk. The glucose and lactose meals emptied in a similar fashion in LA and LM subjects with a significant decrease in gastric emptying as the osmolarity of the meals was doubled. If the data are normalized by dividing lactose emptying by the emptying of glucose meals of twice the osmolality in each individual, the lactose malabsorbers empty significantly more lactose. Both LA and LM subjects emptied comparable amounts of milk meals having similar osmolarity. Chocolate milk, which had a higher osmolality than plain milk, emptied more slowly than plain milk in both groups, and this difference was significant in the LM group.