Effect of a glucagon-like peptide 1 analog, ROSE-010, on GI motor functions in female patients with constipation-predominant irritable bowel syndrome

2012 ◽  
Vol 303 (1) ◽  
pp. G120-G128 ◽  
Author(s):  
Michael Camilleri ◽  
Maria Vazquez-Roque ◽  
Johanna Iturrino ◽  
Amy Boldingh ◽  
Duane Burton ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Gastric Emptying ◽  
Colonic Transit ◽  
Analysis Of Covariance ◽  
Emission Computed Tomography ◽  
Gastric Accommodation ◽  
Female Patients ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Irritable Bowel

The glucagon-like peptide 1 (GLP-1) analog ROSE-010 reduced pain during acute exacerbations of irritable bowel syndrome (IBS). Our objective was to assess effects of ROSE-010 on several gastrointestinal (GI) motor and bowel functions in constipation-predominant IBS (IBS-C). In a single-center, randomized, parallel-group, double-blind, placebo-controlled, dose-response study, we evaluated safety, pharmacodynamics, and pharmacokinetics in female patients with IBS-C. ROSE-010 (30, 100, or 300 μg sc) or matching placebo was administered once daily for 3 consecutive days and on 1 day 2–10 days later. We measured GI and colonic transit by validated scintigraphy and gastric volumes by single-photon emission computed tomography. The primary end points were half time of gastric emptying of solids, colonic transit geometric center at 24 h, and gastric accommodation volume. Analysis included intent-to-treat principle, analysis of covariance (with body mass index as covariate), and Dunnett-Hsu test for multiple comparisons. Exposure to ROSE-010 was approximately dose-proportional across the dose range tested. Demographic data in four treatment groups of female IBS-C patients (total 46) were not different. Gastric emptying was significantly retarded by 100 and 300 μg of ROSE-010. There were no significant effects of ROSE-010 on gastric volumes, small bowel or colonic transit at 24 h, or bowel functions. The 30- and 100-μg doses accelerated colonic transit at 48 h. Adverse effects were nausea ( P < 0.001 vs. placebo) and vomiting ( P = 0.008 vs. placebo). Laboratory safety results were not clinically significant. In IBS-C, ROSE-010 delayed gastric emptying of solids but did not retard colonic transit or alter gastric accommodation; the accelerated colonic transit at 48 h with 30 and 100 μg of ROSE-010 suggests potential for relief of constipation in IBS-C.

scholarly journals Do corticotropin releasing factor-1 receptors influence colonic transit and bowel function in women with irritable bowel syndrome?

2009 ◽  
Vol 296 (6) ◽  
pp. G1299-G1306 ◽  
Author(s):  
Seth Sweetser ◽  
Michael Camilleri ◽  
Sara J. Linker Nord ◽  
Duane D. Burton ◽  
Lorna Castenada ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Colonic Motility ◽  
Bowel Function ◽  
Colonic Transit ◽  
Corticotropin Releasing Factor ◽  
Analysis Of Covariance ◽  
Eligibility Criteria ◽  
Double Blind ◽  
Safety Issues ◽  
Irritable Bowel

Corticotropin releasing factor (CRF), a mediator of stress response, alters gastrointestinal (GI) functions. Stress-related changes in colonic motility are blocked by selective CRF1 receptor antagonists. Our aim was to assess whether modulation of central and peripheral CRF1 receptors affects colonic transit and bowel function in female patients with diarrhea-predominant irritable bowel syndrome (D-IBS). This randomized, double-blind, placebo-controlled, 2-wk study evaluated the effects of oral pexacerfont (BMS-562086), a selective CRF1 receptor antagonist, 25 and 100 mg qd, on GI and colonic transit of solids [by validated scintigraphy with primary end point colonic geometric center (GC) at 24 h] and bowel function (by validated daily diaries) in 39 women with D-IBS. The 100-mg dose was comparable to a dose that inhibited colonic motility in stressed rats. Treatment effects were compared by analysis of covariance with baseline colonic transit as covariate. The study had 80% power (α = 0.05) to detect clinically meaningful (26%) differences in colonic transit. Thirty-nine of 55 patients fulfilled eligibility criteria (9 screen failures, 5 baseline GC24 outside prespecified range). At baseline, three treatment groups had comparable age, body mass index, and GC 24 h. Significant effects of pexacerfont relative to placebo were not detected on colonic GC24 ( P = 0.53), gastric emptying, orocecal transit, ascending colon emptying half-time, and stool frequency, consistency, and ease of passage. No safety issues were identified. We conclude that in women with D-IBS, pexacerfont, 25 or 100 mg qd, does not significantly alter colonic or other regional transit or bowel function. The role of central and peripheral CRF1 receptors in bowel function in D-IBS requires further study.

S1302 Dose-Related Effects of Chenodeoxycholate on Gastrointestinal and Colonic Transit and Bowel Function in Female Patients With Constipation-Predominant Irritable Bowel Syndrome

2010 ◽  
Vol 138 (5) ◽  
pp. S-224
Author(s):  
Archana S. Rao ◽  
Suwebatu T. Odunsi ◽  
Michael Camilleri ◽  
Sanna McKinzie ◽  
Duane D. Burton ◽  
...  
Keyword(s):  
Irritable Bowel Syndrome ◽  
Bowel Function ◽  
Colonic Transit ◽  
Female Patients ◽  
Irritable Bowel

scholarly journals Management of Irritable Bowel Syndrome: Novel Approaches to the Pharmacology of Gut Motility

1999 ◽  
Vol 13 (suppl a) ◽  
pp. 50A-65A ◽  
Author(s):  
Carmelo Scarpignato ◽  
Iva Pelosini
Keyword(s):  
Irritable Bowel Syndrome ◽  
Gastric Emptying ◽  
Contractile Activity ◽  
Normal Function ◽  
Colonic Transit ◽  
Intestinal Transit ◽  
Channel Blockers ◽  
Visceral Perception ◽  
Irritable Bowel ◽  
Gi Motility

Although it is unclear to what extent irritable bowel syndrome (IBS) symptoms represent a normal perception of abnormal function or an abnormal perception of normal function, many believe that IBS constitutes the clinical expression of an underlying motility disorder, affecting primarily the mid- and lower gut. Indeed, transit and contractile abnormalities have been demonstrated with sophisticated techniques in a subset of patients with IBS. As a consequence, drugs affecting gastrointestinal (GI) motility have been widely employed with the aim of correcting the major IBS manifestations, ie, pain and altered bowel function. Unfortunately, no single drug has proven to be effective in treating IBS symptom complex. In addition, the use of some medications has often been associated with unpleasant side effects. Therefore, the search for a truly effective and safe drug to control motility disturbances in IBS continues. Several classes of drugs look promising and are under evaluation. Among the motor- inhibiting drugs, gut selective muscarinic antagonists (such as zamifenacin and darifenacin), neurokinin2 antagonists (such as MEN-10627 and MEN-11420), beta3-adrenoreceptor agonists (eg, SR-58611A) and GI-selective calcium channel blockers (eg, pinaverium bromide and octylonium) are able to decrease painful contractile activity in the gut (antispasmodic effect), without significantly affecting other body functions. Novel mechanisms to stimulate GI motility and transit include blockade of cholecystokinin (CCK)Areceptors and stimulation of motilin receptors. Loxiglumide (and its dextroisomer, dexloxiglumide) is the only CCKAreceptor antagonist that is being evaluated clinically. This drug accelerates gastric emptying and colonic transit, thereby increasing the number of bowel movements in patients with chronic constipation. It is also able to reduce visceral perception. Erythromycin and related 14-member macrolide compounds inhibit the binding of motilin to its receptors on GI smooth muscle and, therefore, act as motilin agonists. This antibiotic accelerates gastric emptying and shortens orocecal transit time. In the large bowel a significant decrease in transit is observed only in the right colon, which suggests a shift in fecal distribution. Several ‘motilinomimetics’ have been synthesized. Their development depends on the lack of antimicrobial activity and the absence of fading of the prokinetic effect during prolonged administration. 5-hydroxytryptamine (5-HT)4agonists with significant pharmacological effects on the mid- and distal gut (such as prucalopride and tegaserod) are available for human use. These ‘enterokinetic’ compounds are useful for treating constipation- predominant IBS patients. 5-HT3receptor antagonists also possess a number of interesting pharmacological properties that may make them suitable for treatment of IBS. Besides decreasing colonic sensitivity to distension, these drugs prolong intestinal transit and may be particularly useful in diarrhea-predominant IBS. Finally, when administered in small pulsed doses, octreotide, besides reducing the perception of rectal distension, accelerates intestinal transit, although other evidence disputes such an effect.

scholarly journals Resveratrol in pandemic: irritable bowel syndrome and obesity

2021 ◽  
pp. 75-83
Author(s):  
А.А. Пальцын ◽  
Н.Б. Свиридкина
Keyword(s):  
Irritable Bowel Syndrome ◽  
Gut Microbiota ◽  
Short Chain Fatty Acids ◽  
Positive Effects ◽  
Anticancer Effects ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Irritable Bowel ◽  
White Fat

Ресвератрол - полифенол, присутствующий во многих ягодах, фруктах, орехах - объект многих тысяч публикаций, в большинстве которых описываются его положительные влияния на различные аспекты здоровья, и даже на продолжительность жизни. В лекции обсуждаются данные о возможности и механизмах профилактического и лечебного действия содержащегося в пище ресвератрола при двух пандемиях: синдроме раздражённого кишечника и ожирении. В публикациях указывается, что около 90% поглощённого с пищей ресвератрола в неизменённом виде достигает толстого кишечника. Здесь ресвератрол включается в метаболизм микробиоты. Бактериологический анализ результатов его действия обнаруживает существенные изменения в количественном соотношении нескольких видов бактерий. Этими изменениями сегодня объясняют многочисленные благоприятные для здоровья результаты приема ресвератрола: стимулируется синтез глюкагоноподобного пептида-1; стимулируется секреция инсулина, снижается концентрация глюкозы в крови; нормализуется липидный обмен; подавляется воспаление; увеличивается синтез короткоцепочечных жирных кислот (бутирата); ускоряется превращение белого жира в бурый. Описаны антиобесогенный, антидиабетический, антиоксидантный, антивоспалительный, антивозрастной, антиатерогенный, антигипертензивный, кардиопротективный, антираковый эффекты ресвератрола. Исследования действия ресвератрола демонстрируют мощное и разностороннее влияние кишечной микробиоты на качество и продолжительность жизни. Resveratrol is a polyphenol found in many berries, fruits, and nuts. It has been addressed in many thousands of publications, most of which describe its positive effects on various aspects of health and even on life expectancy. This review discusses possibilities and mechanisms of preventive and therapeutic actions of dietary resveratrol in two pandemics, irritable bowel syndrome and obesity. It has been reported that about 90% of resveratrol consumed with food reaches the large intestine unchanged and includes into metabolism of the gut microbiota. Bacteriological analysis of the resveratrol effect reveals significant changes in quantitative ratios of several types of bacteria. These changes are currently considered to account for numerous health benefits of resveratrol supplementation, such as stimulation of glucagon-like peptide-1 synthesis and insulin production; decrease in blood glucose; improvement of lipid metabolism; suppression of inflammation; increased synthesis of short-chain fatty acids (butyrate); and accelerated conversion of white fat into brown fat. Also, antiobesity, antidiabetic, antioxidant, anti-inflammatory, anti-aging, anti-atherogenic, antihypertensive, cardioprotective, and anticancer effects of resveratrol are described. Research into the effects of resveratrol demonstrates powerful and versatile effects of gut microbiota on quality of life and longevity.

Effects of glucagon-like peptide-1 (GLP-1) on gastric accommodation, emptying and satiety in humans

2001 ◽  
Vol 120 (5) ◽  
pp. A74-A74
Author(s):  
S AROS ◽  
D KIM ◽  
D BURTON ◽  
G THOMFORDE ◽  
A VELLA ◽  
...  
Keyword(s):  
Gastric Accommodation ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1
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