Acceleration Of Gastric Emptying Research Articles

Do prokinetic agents provide symptom relief through acceleration of gastric emptying? An update and revision ofthe existing evidence.

Gastroparesis and functional dyspepsia are disorders characterized by upper gastrointestinal symptoms and multifaceted etiologies. One of the main therapeutic approaches is accelerating gastric emptying (GE) by means of prokinetic agents. Their efficacy has been demonstrated, although the association between symptom improvement and acceleration of emptying is less clear. Meta-analyses have found contradictory results. Differences in applied methodology and included trials might drive these contradictions. To provide a transparent meta-analysis update to elucidate the association between symptom improvement and acceleration of GE due to gastroprokinetic agents available for long-term use in patients with gastroparesis. Two approaches from earlier meta-analyses were executed and compared. One analyzed the relative changes on active treatment versus baseline, the other compared the change from baseline on active treatment versus the change from baseline on placebo. Papers that reported sufficient numerical data for both analyses were selected. Both analyses included the same trials. Overall, both approaches yield the same positive direction of association between symptom improvement and acceleration of emptying (0.291 (-0.391, 0.972), p=0.4 and 0.453 (0.123, 0.782), p=0.007 for the active-only and placebo-controlled analysis respectively). The association between symptom improvement and GE acceleration for studies using optimal GE tests was either 0.028 (p>0.9) or 0.463 (p=0.007), and for sub-optimal GE tests was either 0.370 (p=0.4) or 0.052 (p>0.9) depending on the used meta-analysis methodology. The applied methodology for GE testing, and the meta-analysis substantially impacts the conclusion. When considering the clinically relevant outcome of improvement from baseline, symptoms and emptying improve with prokinetics, but no correlation is found between both aspects. When the change over placebo is considered, limiting the analysis to scientifically more rigorous study approaches, changes in emptying rate and symptom improvement are positively associated.

Gastric Electrical Stimulation: Role and Clinical Impact on Chronic Nausea and Vomiting.

Gastric electrical stimulation (GES) is currently used as an alternative treatment for medically refractory gastroparesis. GES has been initially developed to accelerate gastric motility, in order to relieve the symptoms of the patients. Subsequent studies, unfortunately, failed to demonstrate the acceleration of gastric emptying using high-frequency stimulation – low energy stimulation although the technique has shown a clinical impact with a reduction of nausea and vomiting for patients with gastroparesis. The present review details the clinical efficacy of GES in gastroparesis as well as its putative mechanisms of action.

New Drugs on the Horizon for Functional and Motility Gastrointestinal Disorders

New Drugs on the Horizon for Functional and Motility Gastrointestinal Disorders

Acceleration of Gastric Emptying by Insulin-Induced Hypoglycemia is Dependent on the Degree of Hypoglycemia.

Hypoglycemia is a major barrier to optimal glycemic control in insulin-treated diabetes. Recent guidelines from the American Diabetes Association have subcategorized "non-severe" hypoglycemia into level 1 (<3.9 mmol/L) and 2 (<3 mmol/L) hypoglycemia. Gastric emptying of carbohydrate is a major determinant of postprandial glycemia but its role in hypoglycemia counter-regulation remains underappreciated. "Marked" hypoglycemia (~2.6 mmol/L) accelerates gastric emptying and increases carbohydrate absorption in health and type 1 diabetes, but the impact of "mild" hypoglycemia (3.0-3.9 mmol/L) is unknown. To determine the effects of 2 levels of hypoglycemia, 2.6 mmol/L ("marked") and 3.6 mmol/L ("mild"), on gastric emptying in health. Fourteen healthy male participants (mean age: 32.9 ± 8.3 years; body mass index: 24.5 ± 3.4 kg/m2) from the general community underwent measurement of gastric emptying of a radiolabeled solid meal (100 g beef) by scintigraphy over 120 minutes on 3 separate occasions, while blood glucose was maintained at either ~2.6 mmol/L, ~3.6 mmol/L, or ~6 mmol/L in random order from 15 minutes before until 60 minutes after meal ingestion using glucose-insulin clamp. Blood glucose was then maintained at 6 mmol/L from 60 to 120 minutes on all days. Gastric emptying was accelerated during both mild (P = 0.011) and marked (P = 0.001) hypoglycemia when compared to euglycemia, and was more rapid during marked compared with mild hypoglycemia (P = 0.008). Hypoglycemia-induced gastric emptying acceleration during mild (r = 0.57, P = 0.030) and marked (r = 0.76, P = 0.0014) hypoglycemia was related to gastric emptying during euglycemia. In health, acceleration of gastric emptying by insulin-induced hypoglycemia is dependent on the degree of hypoglycemia and baseline rate of emptying.

S1350 Relation of Increased Pyloric Diameter and Distensibility Measured by EndoFLIP to Improved Gastric Emptying After G-POEM for Refractory Gastroparesis

INTRODUCTION: Gastric per-oral endoscopic myotomy (G-POEM) to treat gastroparesis works by decreasing pyloric outlet obstruction. G-POEM is effective in some, but not all patients, suggesting multiple causes of gastric emptying delay. Impedance planimetry with EndoFLIP (Functional Lumen Imaging Probe) measures pyloric function before and after G-POEM. The relation of improvements in pyloric functional parameters to acceleration of gastric emptying after G-POEM is unproven. We compared EndoFLIP measurements of pyloric diameter and distensibility after endoscopic myotomy to normalization of gastric emptying rates in an initial series of patients with refractory gastroparesis who underwent G-POEM. METHODS: 13 patients with refractory gastroparesis underwent gastric emptying scintigraphy before and after G-POEM. Pyloric EndoFLIP was conducted with balloon inflation to 30-50mL. Pre- and post-myotomy mean pyloric diameter and distensibility were compared in those without and with normalization of gastric emptying (< 10% 4 hr scintigraphic retention) performed approximately 3 months after G-POEM. RESULTS: Gastric emptying was normal after G-POEM in 5 patients (4 hr retention 4 ± 4%) and abnormal in 8 patients (4 hr retention 27 ± 23%) (P = 0.05). In the whole group, mean pyloric diameter increased from 13.5 ± 2.1 to 16.2 ± 2.7mm on 40 mL inflation (P < 0.0001) and distensibility increased from 5.1 ± 1.8 to 8.2 ± 4.6mm2/mmHg on 50mL inflation (P = 0.01). Figure 1 shows similar antropyloroduodenal diameters in relation to gastric emptying normalization before and after G-POEM. Increases in pyloric diameter were not different in those with normal vs. abnormal gastric emptying (3.3 ± 1.1 vs. 1.4 ± 1.7mm) (P = 0.25). Figure 2 shows that pre- and post-myotomy pyloric distensibility and increases in distensibility were similar in those with normal vs. abnormal gastric emptying after G-POEM. CONCLUSION: Mean pyloric diameter and distensibility measured by EndoFLIP increased after G-POEM for refractory gastroparesis. These increases were similar in patients who normalized their gastric emptying after myotomy compared to those who did not. This raises the possibility of two gastroparesis subtypes—patients primarily with pyloric dysfunction who respond to G-POEM and those who do not respond who likely have primary antral or fundic impairments. Confirmation of these initial findings will require larger cohorts.Figure 1.: Pre- and post-myotomy antropyloroduodenal diameters measured by EndoFLIP were similar in patients who had normal vs. abnormal gastric emptying after G-POEM.Figure 2.: Distensibility pre- and post-myotomy and net increases in distensibility after myotomy were similar in patients who had normal vs. abnormal gastric emptying after G-POEM.

Win 55,212-2, atenolol and subdiaphragmatic vagotomy prevent acceleration of gastric emptying induced by cachexia via Yoshida-AH-130 cells in rats

The aim of this study was to investigate the effect of cachexia induced by AH-130 cells on gastrointestinal motility in rats. We evaluated food intake, body weight variation, cachexia index, gastric emptying and in vitro gastric responsiveness of control or cachexia rats. In addition, we evaluated the effect of pretreatment with atenolol (20 mg/kg, p.o.), win 55,212-2 (2 mg/kg, s.c.) or subdiaphragmatic vagotomy on the effects found. Atenolol prevented (P < 0.05) the acceleration of gastric emptying (area under the curve, AUC, 20360.17 ± 1970.9 vs. 12579.2 ± 785.4 μg/min/ml), and increased gastric responsiveness to carbachol (CCh) stimulation in cachectic rats compared to control groups (CCh-6M: 63.2 ± 5.5% vs. 46.5 ± 5.7%). Vagotomy prevented (P < 0.05) increase in gastric emptying acceleration (AUC 20360.17 ± 1970.9 vs. 13414.0 ± 1112.9 μg/min/ml) and caused greater in vitro gastric responsiveness of cachectic compared to control rats (CCh-6M: 63.2 ± 5.5% vs. 31.2 ± 4.7%). Win 55,212-2 attenuated the cachexia index (38.5 ± 2.1% vs. 25.8 ± 2.7%), as well as significantly (P < 0.05) preventing increase in gastric emptying (AUC 20360.17 ± 1970.9 vs. 10965.4 ± 1392.3 μg/min/ml) and gastric responsiveness compared to control groups (CCh-6M: 63.2 ± 5.5% vs. 38.2 ± 3.9%). Cachexia accelerated gastric emptying and increased gastric responsiveness in vitro. These phenomena were prevented by subdiaphragmatic vagotomy and by atenolol and win 55,212-2 treatments, showing vagal involvement of β1-adrenergic and cannabinoid CB1/CB2 receptors.

Acceleration of Gastric Emptying and Improvement of GERD Outcome After Laparoscopic Sleeve Gastrectomy in Non-diabetic Obese Patients.

Obesity has become a pandemic nowadays. Bariatric surgery is increasingly performed to manage obesity. Currently, laparoscopic sleeve gastrectomy (LSG) is a widely accepted procedure given its feasibility and efficacy. Previous studies revealed conflicting results regarding the change of gastric emptying following sleeve gastrectomy. The primary aim of the present study is to assess gastric motor function by gastric emptying scintigraphy in a cohort of non-diabetic patients undergoing laparoscopic sleeve gastrectomy (LSG) for treatment of severe obesity. This prospective observational study included 100 obese, non-diabetic patients attending the surgery clinic at Cairo University Hospitals and Al Azhar University Hospitals. LSG was performed following a standardized protocol, with no complications observed. All patients had gastric emptying scintigraphy done through a standard semisolid meal (250kcal), marked with 0.5 mCiTc 99, pre-operatively and 3months after LSG. The mean age was 38.71years (9.2) and males comprised 57% of the cohort. The body mass index, low-density lipoproteins, and glycated hemoglobin declined significantly at 3-month postsurgery. The scintigraphy study revealed a significantly reduced percent retention at equivalent time points 3months after LSG. In addition, the percent of patients suffering from GERD decreased significantly after LSG. Gastric emptying becomes faster after LSG in morbidly obese non-diabetic patients. GERD symptoms improve after surgery.

Scintigraphic evaluation of gastric emptying after greater curvature plication in comparison with sleeve gastrectomy

Introduction: Laparoscopic gastric plication (LGP) is a relatively new restrictive bariatric procedure that emerged to avoid the problems and to reduce the cost of laparoscopic sleeve gastrectomy. In this study we present the initial short-term outcome of LGP and its effect on gastric emptying and compare it with the results of laparoscopic sleeve gastrectomy (LSG). Methods: From May 2016 to April 2017, a total of 50 patients were allocated to undergo either LGP (n = 25) or LSG (n = 25). Data on the operative time, complications, hospital stay, overall cost of LSG and LGCP, body mass index loss (BMIL), post-operative gastric emptying (the first study to asses gastric emptying after LGP), percentage of excess weight loss (%EWL), and improvement of comorbidities were collected during the follow-up examinations. Results: All procedures were completed laparoscopically. The mean operative time was significantly higher for the LGP group. The mean hospital stay, cost and %EWL were significantly higher in the LSG group. The mean gastric emptying t1/2 was 40 ± 13 minutes for LGP group and 28.3 ± 8.31 minutes for LSG group (P = 0.001). Conclusion: There is significant acceleration of gastric emptying after LSG more than after LGP with significant effect on weight loss.

Alpha-melanocyte stimulating hormone in ghrelin-elicited feeding and gut motility.

This review evaluates published studies regarding alpha-melanocyte stimulating hormone (α-MSH) in ghrelin-elicited feeding and gut motility. We have sought to integrate all available evidences to provide a complete review on the properties of melanocortin receptors (MCR) and the potential clinical treatment of α-MSH after ghrelin-elicited feeding and gut motility. The available studies were grouped into four categories: food intake, gastric emptying, small intestinal transit, and colonic transit. As we describe, the literature provides evidence of the ability of ghrelin to increase food intake, gastric emptying, small intestinal transit, and colonic transit. α-MSH, which displays high affinity for the MC3 and MC4 receptors, can competitively activate MCRs with agouti-related protein stimulated by ghrelin, and partly attenuates the effect of acyl ghrelin on food intake. Central ghrelin-induced acceleration of gastric emptying is not mediated by MCRs, but the acceleration of the small intestinal transit is at least partly mediated via MCRs in the brain. Similar to fecal pellets and total fecal weight, distal colonic motility and secretion are partly mediated by MCRs in the brain. The interplay between acyl ghrelin and MCRs may provide a new therapeutic avenue to ameliorate anorexia and constipation.

Hypoglycaemia and gastric emptying.

Hypoglycaemia is arguably the most important complication of insulin therapy in type 1 and type 2 diabetes. Counter-regulation of hypoglycaemia is dependent on autonomic function and frequent hypoglycaemia may lead to reductions in both autonomic warning signals and the catecholamine response, the so-called "impaired awareness of hypoglycaemia". It is now appreciated that gastric emptying is a major determinant of the glycaemic response to carbohydrate-containing meals in both health and diabetes, that disordered (especially delayed) gastric emptying occurs frequently in diabetes, and that acute hypoglycaemia accelerates gastric emptying substantially. However, the potential relevance of gastric emptying to the predisposition to, and counter-regulation of, hypoglycaemia has received little attention. In insulin-treated patients, the rate of gastric emptying influences the timing of the postprandial insulin requirement, and gastroparesis is likely to predispose to postprandial hypoglycaemia. Conversely, the marked acceleration of gastric emptying induced by hypoglycaemia probably represents an important counter-regulatory response to increase the rate of carbohydrate absorption. This review summarizes the current knowledge of the inter-relationships between hypoglycaemia and gastric emptying, with a focus on clinical implications.

α-melanocyte stimulating hormone modulates the central acyl ghrelin-induced stimulation of feeding, gastrointestinal motility, and colonic secretion.

BackgroundAcyl ghrelin-induced intake depends on hypothalamic neuropeptide Y and agouti-related protein (AgRP) neurotransmitters. Intracerebroventricular (ICV) injection of AgRP increases feeding through competitive antagonism at melanocortin receptors. ICV administration of α-melanocyte stimulating hormone (α-MSH), a natural antagonist of AgRP, may modulate the acyl ghrelin-induced orexigenic effect.ObjectiveThis study aimed to investigate the modulating effect of α-MSH on the central acyl ghrelin-induced food intake, gastrointestinal motility, and colonic secretion in rats.Methods and proceduresWe examined the effects of α-MSH and acyl ghrelin on food intake, gastric emptying, small intestinal transit, colonic motility, and secretion in conscious rats with a chronic implant of ICV catheters.ResultsICV injection of O-n-octanoylated ghrelin (0.1 nmol/rat) significantly increased the cumulative food intake up to 8 h (P<0.01), enhanced non-nutrient semi-liquid gastric emptying (P<0.001), increased the geometric center and running percentage of small intestinal transit (P<0.001), accelerated colonic transit time (P<0.05), and increased fecal pellet output (P<0.01) and total fecal weight (P<0.01). Pretreatment with ICV injection of α-MSH (1.0 and 2.0 nmol/rat) attenuated the acyl ghrelin-induced hyperphagic effect, fecal pellet output, and total fecal weight, while higher dose of α-MSH (2.0 nmol/rat) attenuated the increase in the geometric center of small intestinal transit (P<0.01). However, neither dose of α-MSH altered acyl ghrelin-stimulated gastroprokinetic effect, increase in the running percentage of small intestinal transit, nor accelerated colonic transit time.Conclusionα-MSH is involved in central acyl ghrelin-elicited feeding, small intestinal transit, fecal pellet output, and fecal weight. α-MSH does not affect central acyl ghrelin-induced acceleration of gastric emptying and colonic transit time in rats.

Antecedent Hypoglycemia Does Not Attenuate the Acceleration of Gastric Emptying by Hypoglycemia.

Acute hypoglycemia accelerates gastric emptying and increases cardiac contractility. However, antecedent hypoglycemia attenuates counterregulatory hormonal responses to subsequent hypoglycemia. To determine the effect of antecedent hypoglycemia on gastric and cardiac responses to subsequent hypoglycemia in health. A prospective, single-blind, randomized, crossover study (performed at the Royal Adelaide Hospital, Adelaide, South Australia, Australia). Ten healthy young men 18 to 35 years of age were studied for 36 hours on two occasions. Participants were randomly assigned to either antecedent hypoglycemia [three 45-minute periods of strict hypoglycemia (2.8 mmol/L] or control [three 45-minute periods of strict euglycemia (6 mmol/L)] during the initial 12-hour period. Participants were monitored overnight, and the following morning blood glucose was clamped at 2.8 mmol/L for 60 minutes and then at 6 mmol/L for 120 minutes. At least 6 weeks later participants returned for the alternative intervention. Gastric emptying and cardiac fractional shortening were measured with scintigraphy and two-dimensional echocardiography, respectively, on the morning of all 4 study days. A single, acute episode of hypoglycemia accelerated gastric emptying (P = 0.01) and augmented fractional shortening (P < 0.01). Gastric emptying was unaffected by antecedent hypoglycemia (P = 0.74) whereas fractional shortening showed a trend to attenuation (P = 0.06). The adrenaline response was diminished (P < 0.05) by antecedent hypoglycemia. In health, the acceleration of gastric emptying during hypoglycemia is unaffected by antecedent hypoglycemia, whereas the increase in cardiac contractility may be attenuated.

Alteraciones motoras gástricas

IntroductionThe stomach is the segment of the gastrointestinal tract where they start the main functions of secretion and gastrointestinal digestion. PathophysiologyHowever, the most critical and important in the digestive physiology gastric function is given by its motor activity, which allows storage, starting the process of crushing, digestion and emptying/progression of food to the rest of the digestive tract. Alterations in this complex coordination process can lead to changes in gastric emptying. GastroparesisAlthough there are pathologies in which an acceleration of gastric emptying, motor dysfunction delay is the predominant and for this reason is the one that occupies much of this review takes place.

The effect of Flos Lonicerae Japonicae extract on gastro-intestinal motility function

Ethnopharmacological relevanceFlos Lonicerae Japonicae is a well-known herb of traditional Chinese medicine that has been used for heat-clearing, detoxification, anti-inflammation, throat pain and gastro-intestinal (GI) disorder. In order to verify the effect of Flos Lonicerae Japonicae on GI disorder, we investigated the prokinetic effect of GC-7101 on GI motility function. Materials and methodsGC-7101 is the standardized extract of Flos Lonicerae Japonicae. The contractile action of GC-7101 on feline esophageal smooth muscle cell (ESMC) was evaluated by measuring dispersed cell length. The isometric tension study was performed to investigate the effect of GC-7101 on feline lower esophageal sphincther (LES). The prokinetic effect of GC-7101 was investigated by gastric emptying (GE) and gastro-intestinal transit (GIT) in rats. ResultsGC-7101 produced concentration-dependent contractions in ESMCs. Pretreatment with 5-HT3 and 5-HT4 receptor blocker (ondansetron and GR113808) inhibited the contractile responses of the GC-7101-induced ESMCs. In isometric tension study, GC-7101 recovered the HCl-induced decreased tone of LES muscle strips. The treatment of GC-7101 enhanced the carbachol-induced contractile responses and the electric field stimulation (EFS)-induced on-contraction. The oral administration of GC-7101 not only significantly accelerated GE and GIT in normal rats but also recovered the delayed GE and GIT, and its effect was more potent than that of conventional prokinetics (e.g., domperidone, a dopamine-receptor antagonist, and mosapride, a 5-HT4-receptor agonist). ConclusionGC-7101 revealed a prokinetic effect through enhancing the contractile responses of ESMCs, tone increases, enhancing the carbarchol- or EFS-induced contractile responses of LES muscle strips, and the acceleration of GE and GIT. We have identified the significant potential of GC-7101 for the development of new prokinetic drugs through this study.

Pyloroplasty for Refractory Gastroparesis

Gastroparesis is a chronic gastric motility disorder in which the pathophysiology mimics a postvagotomy state. Pyloroplasty is beginning to emerge as a successful drainage procedure for refractory gastroparesis. Here we report our experience using pyloroplasty in the surgical management of diabetic and nondiabetic gastroparesis. A retrospective study was performed of 46 patients undergoing pyloroplasty for refractory gastroparesis from January 2010 through December 2013. Gastric emptying scintigraphy and the Gastroparesis Cardinal Symptom Index were assessed pre- and postoperatively. Laparoscopic pyloroplasty was performed in 42 patients, open pyloroplasty in three, and one patient was converted from laparoscopic to open pyloroplasty. Studies were repeated during the six to 12 month postoperative interval. The postoperative gastric emptying scintigraphy improved in 90 per cent of patients and normalized in 60 per cent. Postoperative T½ was significantly reduced (P = 0.001) as was four-hour retention (P < 0.001). The Gastroparesis Cardinal Symptom Index showed statistically significant reduction in symptom severity for all nine categories (P < 0.0005) as well as total symptom score (P < 0.005). No patients developed dumping syndrome. Pyloroplasty is a highly effective therapy for refractory gastroparesis, offering significant reduction in symptom severity, improvement in quality of life, and acceleration of gastric emptying.

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Emerging treatments in Neurogastroenterology: relamorelin: a novel gastrocolokinetic synthetic ghrelin agonist.

Synthetic ghrelin agonists, predominantly small molecules, are being developed as prokinetic agents that may prove useful in the treatment of gastrointestinal motility disorders. Relamorelin (RM-131) is a pentapeptide synthetic ghrelin analog that activates the growth hormone secretagogue (GHS)-1a (also called the ghrelin) receptor with approximately sixfold greater potency than natural ghrelin. The ability of relamorelin to stimulate growth hormone (GH) release is comparable to that of native ghrelin. Relamorelin has enhanced efficacy and plasma stability compared to native ghrelin. In this review, we discuss the pharmacokinetics, pharmacodynamics and potential indications for relamorelin. Relamorelin is administered subcutaneously, dosed daily or twice daily. Relamorelin is being studied for the treatment of patients with gastrointestinal motility disorders. Phase IIA pharmacodynamic studies have demonstrated acceleration of gastric emptying in patients with type 1 diabetes mellitus (T1DM) and type 2 DM (T2DM) and upper gastrointestinal symptoms. In a phase IIA study in patients with diabetic gastroparesis, relamorelin accelerated gastric emptying and significantly improved vomiting frequency compared to placebo and improved other symptoms of gastroparesis in a prespecified subgroup of patients with vomiting at baseline. In patients with chronic idiopathic constipation with defined transit profile at baseline, relamorelin relieved constipation and accelerated colonic transit compared to placebo. These characteristics suggest that this new ghrelin analog shows great promise to relieve patients with upper or lower gastrointestinal motility disorders.

Glucagon-Like Peptide 1 Attenuates the Acceleration of Gastric Emptying Induced by Hypoglycemia in Healthy Subjects

Exogenous GLP-1 slows gastric emptying in health and diabetes leading to diminished glycemic excursions. Gastric emptying is markedly accelerated by hypoglycemia. The primary objective was to determine whether GLP-1 attenuates the acceleration of gastric emptying induced by hypoglycemia. Ten healthy volunteers were studied on four separate days in a randomized double-blind fashion. Blood glucose was stabilized using a glucose/insulin clamp at hypoglycemia (2.6 mmol/L on two occasions [hypo]) or euglycemia (6.0 mmol/L on two occasions [eu]) between T = -15 and 45 min before clamping at 6.0 mmol/L until 180 min. During hypoglycemia and euglycemia, subjects received intravenous GLP-1 (1.2 pmol/kg/min) or placebo. At T = 0 min, subjects ingested 100 g beef mince labeled with 20 MBq (99m)Tc-sulfur-colloid and 3 g of 3-O-methyl-glucose (3-OMG), a marker of glucose absorption. Gastric emptying was measured scintigraphically from T = 0 to 180 min and serum 3-OMG taken at 15-min intervals. The areas under the curve for gastric emptying and 3-OMG concentration were analyzed using one-way repeated-measures ANOVA with Bonferroni-Holm adjusted post hoc tests. Gastric emptying was accelerated during hypoglycemia (hypo/placebo vs. eu/placebo; P < 0.001), as was glucose absorption (P < 0.03). GLP-1 slowed emptying during euglycemia (eu/placebo vs. eu/GLP-1; P < 0.001). However, hypoglycemia-induced acceleration of gastric emptying on placebo was markedly diminished by GLP-1 (hypo/placebo vs. hypo/GLP-1; P < 0.008), as was glucose absorption (P < 0.01). Acute administration of exogenous GLP-1 attenuates, but does not abolish, the acceleration of gastric emptying by insulin-induced hypoglycemia in healthy subjects.

Detection of drug effects on gastric emptying and contractility using a wireless motility capsule.

BackgroundA wireless motility capsule is a new method for ambulatory assessment of transit times and motility throughout the gastrointestinal tract. The objective of this study was to evaluate the ability of a wireless motility capsule to detect drug effects on gastric emptying time (GET) and gastric contractility.Methods15 healthy adults were administered in random order saline, erythromycin IV 150 mg, or morphine IV 0.05 mg/kg BW. Subjects ate a standard meal after each infusion, and subsequently ingested the motility capsule. Data were recorded for 8 hours, and the results were analyzed using the manufacturer’s software.ResultsGET was significantly faster after erythromycin than either saline or morphine. Morphine tended to delay emptying of the capsule compared to saline. There was a trend toward a greater frequency of gastric contractions with erythromycin and a reduced frequency of gastric contractions with morphine that did not reach statistical significance.ConclusionsA wireless motility capsule successfully detected acceleration of gastric emptying induced by erythromycin, and retardation of gastric motility caused by morphine. These results indicate that a wireless motility capsule is a promising technique to assess pharmacologic effects on gastric transit and contractility and aid in development of drugs for gastric motor disorders.

Motilin: towards a new understanding of the gastrointestinal neuropharmacology and therapeutic use of motilin receptor agonists.

The gastrointestinal hormone motilin has been known about for >40 years, but after identification of its receptor and subsequent development of new tools and methods, a reappraisal of its actions is required. Firstly, it is important to note that motilin and ghrelin receptors are members of the same family (similar genomic organization, gastrointestinal distribution and abilities to stimulate gastrointestinal motility), yet each fails to recognize the ligand of the other; and whereas ghrelin and ghrelin receptors are widespread outside the gastrointestinal tract, motilin and its receptors are largely restricted to the gastrointestinal tract. Secondly, although some studies suggest motilin has activity in rodents, most do not, and receptor pseudogenes exist in rodents. Thirdly, motilin preferentially operates by facilitating enteric cholinergic activity rather than directly contracting the muscle, despite the relatively high expression of receptor immunoreactivity in muscle. This activity is ligand-dependent, with short-lasting actions of motilin contrasting with longer-lasting actions of the non-selective and selective motilin receptor agonists erythromycin and GSK962040. Finally, the use of erythromycin (also an antibiotic drug) to treat patients requiring acceleration of gastric emptying has led to concerns over safety and potential exacerbation of antibiotic resistance. Replacement motilin receptor agonists derived from erythromycin (motilides) have been unsuccessful. New, non-motilide, small molecule receptor agonists, designed to minimize self-desensitization, are now entering clinical trials for treating patients undergoing enteral feeding or with diabetic gastroparesis. Thus, for the translational pharmacologist, the study of motilin illustrates the need to avoid overreliance on artificial systems, on structural information and on animal studies. This article is part of a themed section on Neuropeptides. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2013.170.issue-7.