Functional Gastrointestinal Disorders
Conditions
Keywords
Irritable bowel syndrome, Functional dyspepsia, Gastric emptying, Gastrointestinal peptide hormones
Brief summary
The inhibitory effect of low dose GLP-1 is investigated on prandial motility of the stomach, duodenum and jejunum in vivo in humans. Supplementary in vitro studies on the mechanism of action of the GLP-1 inhibition of motility as carried out on muscle strips from the upper gastrointestinal tract in man.
Detailed description
Twelve healthy volunteers will undergo antroduodenojejunal manometry. Baseline recording with infusion of saline for 1 hour is compared with infusion of GLP-1 0.7 and 1.2 pmol per kg minute for another 1 hour. Plasma GLP-1 and GLP-2 is measured by RIA. Responses to GLP-1 will be measured after food intake as prandial response to GLP-1. The outcome will be evaluated as change in motility index from baseline to meal-stimulated conditions and during influence of GLP-1. Further in vitro studies of gastrointestinal muscle strips, precontracted with bethanechol or electric field stimulation, are planned to investigate the response to GLP-1 or GLP-1 analogue ROSE-010. GLP-1 and GLP-2 receptor immunoreactivity is localized by immunohistochemistry. Receptor mediated mechanisms are studied with GLP-1 receptor blocker exendin(9-39)amide, nitro-monomethyl arginine to block nitric oxide synthase and tetrodotoxin to block sodium channels and nerve conduction.
Interventions
BIOLOGICALGLP-1
Intravenous infusion of GLP-1
BIOLOGICALIntravenous saline
Control
Sponsors
Karolinska Institutet
Uppsala University
Study design
Allocation
NON_RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy volunteers over 18 years of age.
Exclusion criteria
* Any medical condition. * Any drug treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Motility index (measure of contraction amplitude x duration; area for mmHg x sec) | 60 minutes | Inhibition of prandially increased motility index (motor activity in the antrum and upper small intestine). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Smooth muscle relaxation induced by GLP-1 | 6 hours | Separate experiments in vitro: GLP-1-induced inhibition of bethanechol-stimulated smooth muscle strips to characterize GLP-1's pharmacological action. |
| Presence of GLP-1 and GLP-2 receptors in gastric and small bowel tissue | 1 day | Separate experiments in vitro: Antibody staining of gastric and small bowel tissue for receptors of GLP-1 and GLP-2 |
Countries
Sweden
Outcome results
None listed