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| Name | Class |
|---|---|
| Karolinska Institutet | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| GLP-1 | Experimental | Intravenous infusion of GLP-1 at 0.7 and 1.2 mol/kg per minute |
|
| Control | Placebo Comparator | Intravenous saline |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| GLP-1 | Biological | Intravenous infusion of GLP-1 |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| 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). | 60 minutes |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 6 hours |
| Presence of GLP-1 and GLP-2 receptors in gastric and small bowel tissue |
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Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Per M. Hellström, MD, PhD | Uppsala University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Uppsala University | Uppsala | Uppsala County | 75185 | Sweden |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20584260 | Background | Edholm T, Degerblad M, Gryback P, Hilsted L, Holst JJ, Jacobsson H, Efendic S, Schmidt PT, Hellstrom PM. Differential incretin effects of GIP and GLP-1 on gastric emptying, appetite, and insulin-glucose homeostasis. Neurogastroenterol Motil. 2010 Nov;22(11):1191-200, e315. doi: 10.1111/j.1365-2982.2010.01554.x. | |
| 18945254 | Background |
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On request.
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| ID | Term |
|---|---|
| D005767 | Gastrointestinal Diseases |
| D043183 | Irritable Bowel Syndrome |
| ID | Term |
|---|---|
| D004066 | Digestive System Diseases |
| D003109 | Colonic Diseases, Functional |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
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| ID | Term |
|---|---|
| D052216 | Glucagon-Like Peptide 1 |
| ID | Term |
|---|---|
| D004763 | Glucagon-Like Peptides |
| D052336 | Proglucagon |
| D005768 | Gastrointestinal Hormones |
| D006728 | Hormones |
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| Intravenous saline | Biological | Control |
|
Separate experiments in vitro: Antibody staining of gastric and small bowel tissue for receptors of GLP-1 and GLP-2 |
| 1 day |
| Hellstrom PM, Hein J, Bytzer P, Bjornsson E, Kristensen J, Schambye H. Clinical trial: the glucagon-like peptide-1 analogue ROSE-010 for management of acute pain in patients with irritable bowel syndrome: a randomized, placebo-controlled, double-blind study. Aliment Pharmacol Ther. 2009 Jan;29(2):198-206. doi: 10.1111/j.1365-2036.2008.03870.x. Epub 2008 Oct 10. |
| 18298441 | Result | Hellstrom PM, Naslund E, Edholm T, Schmidt PT, Kristensen J, Theodorsson E, Holst JJ, Efendic S. GLP-1 suppresses gastrointestinal motility and inhibits the migrating motor complex in healthy subjects and patients with irritable bowel syndrome. Neurogastroenterol Motil. 2008 Jun;20(6):649-59. doi: 10.1111/j.1365-2982.2007.01079.x. Epub 2008 Feb 19. |
| 29177486 | Derived | Halim MA, Degerblad M, Sundbom M, Karlbom U, Holst JJ, Webb DL, Hellstrom PM. Glucagon-Like Peptide-1 Inhibits Prandial Gastrointestinal Motility Through Myenteric Neuronal Mechanisms in Humans. J Clin Endocrinol Metab. 2018 Feb 1;103(2):575-585. doi: 10.1210/jc.2017-02006. |
| D006730 |
| Hormones, Hormone Substitutes, and Hormone Antagonists |