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GLP-1 acts at myent...
GLP-1 acts at myenteric neurons to inhibit motility in humans: results of in vivo motility studies and in vitro characterization of responses to GLP-1 and ROSE-010 : GLP-1 and digestive motility
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- Halim, Md Abdul (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Uppsala University,Gastroenterology & Hepatology
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- Marie, Degerblad (author)
- Karolinska Institutet,Growth and Metabolism
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- Magnus, Sundbom (author)
- Uppsala universitet,Institutionen för kirurgiska vetenskaper,Uppsala University
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- Dominic-Luc, Webb (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Uppsala University,Gastroenterology & Hepatology
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- Per, Hellström (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Uppsala University,Gastroenterology & Hepatology
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(creator_code:org_t)
- English.
- Related links:
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https://urn.kb.se/re...
Abstract
Subject headings
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- Background: Glucagon-like peptide-1 (GLP-1) is secreted from L-cells after nutrient ingestion, inhibiting motility. Aims: To clarify whether infused GLP-1 inhibits in vivo prandial motility response and determine the likeliest target cell type and mechanism of action of GLP-1 and its analogue ROSE-010 using in vitro human gut muscle strips. Methods: Sixteen healthy volunteers underwent antroduodenojejunal manometry. Recordings of 1 hour infusion of saline or GLP-1 (0.7 or 1.2 pmol/kg/min) were compared. Plasma GLP-1 and GLP-2 were measured by RIA. Gastrointestinal muscle strips from surgical re-sections, pre-contracted with bethanechol or electric field stimulation (EFS), were investigated for GLP-1 or ROSE-010 induced relaxation. Receptors for GLP-1 and GLP-2 (GLP-1R, GLP-2R) were visualized by immunohistochemistry. Mechanisms were studied employing exendin(9-39) amide, Lw-nitro-monomethyl arginine (L-NMMA), 2´5´-dideoxyadenosine (DDA) and tetrodotoxin (TTX). Results: Food-intake increased motility index from 4.0±0.5 to 6.4±0.3 (antrum), 4.2±0.4 to 5.7±0.4 (duodenum) and 4.6±0.3 to 5.9±0.2 (jejunum) ln(Σ(mmHg·s·min-1)). GLP-1 at 0.7 pmol/kg/minwas sufficient to suppress these indexes from 6.2±0.4 to 3.8±0.7, 5.6±0.6 to 3.9±0.6 and 5.8±0.1 to 4.6±0.4 ln(Σ(mmHg·s·min-1)). Both GLP-1 doses raised plasma GLP-1, but not GLP-2. GLP-1 (EC50 40 nM) and ROSE-010 (EC50 50 nM) relaxed bethanechol-induced contractions in muscle strips. Inhibitory responses were blocked by exendin(9-39) amide, L-NMMA, DDA or TTX pre-treatment. GLP-1R and GLP-2R were expressed in myenteric neurons, but not muscle. Conclusions: GLP-1 and ROSE-010 inhibit motility through GLP-1R at myenteric neurons, which also possess GLP-2 receptors. GLP-1 increases more than GLP-2 with meals and does not increase plasma GLP-2. GLP-1 and ROSE-010 relaxations are cAMP and NO dependent.
Keyword
- Antroduodenojejunal motility
- Glucagon-like peptides
- Peptide hormones
- ROSE-010
- exendin(9-39) amide
- Physiology
- Fysiologi
Publication and Content Type
- vet (subject category)
- ovr (subject category)
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