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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
SINGLE
Enrollment
12
Intravenous infusion of GLP-1
Control
Uppsala University
Uppsala, Uppsala County, Sweden
Motility index (measure of contraction amplitude x duration; area for mmHg x sec)
Inhibition of prandially increased motility index (motor activity in the antrum and upper small intestine).
Time frame: 60 minutes
Smooth muscle relaxation induced by GLP-1
Separate experiments in vitro: GLP-1-induced inhibition of bethanechol-stimulated smooth muscle strips to characterize GLP-1's pharmacological action.
Time frame: 6 hours
Presence of GLP-1 and GLP-2 receptors in gastric and small bowel tissue
Separate experiments in vitro: Antibody staining of gastric and small bowel tissue for receptors of GLP-1 and GLP-2
Time frame: 1 day
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