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Sökning: onr:"swepub:oai:DiVA.org:uu-294388" > 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

Halim, Md Abdul, (författare)
Uppsala universitet, Institutionen för medicinska vetenskaper, Uppsala University, Gastroenterology & Hepatology
Marie, Degerblad, (författare)
Karolinska Institutet, Growth and Metabolism
Magnus, Sundbom, (författare)
Uppsala universitet, Institutionen för kirurgiska vetenskaper, Uppsala University
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Dominic-Luc, Webb, (författare)
Uppsala universitet, Institutionen för medicinska vetenskaper, Uppsala University, Gastroenterology & Hepatology
Per, Hellström, (författare)
Uppsala universitet, Institutionen för medicinska vetenskaper, Uppsala University, Gastroenterology & Hepatology
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Uppsala universitet Medicinska och farmaceutiska vetenskapsområdet. Medicinska fakulteten. Institutionen för medicinska vetenskaper. (creator_code:org_t)
Uppsala universitet Medicinska och farmaceutiska vetenskapsområdet. Medicinska fakulteten. Institutionen för kirurgiska vetenskaper. (creator_code:org_t)
language:D_t.
  • Annan publikation (övrigt vetenskapligt)
Abstract Ämnesord
Stäng  
  • 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  (hsv//swe)
MEDICAL AND HEALTH SCIENCES  (hsv//eng)

Nyckelord

Antroduodenojejunal motility
Glucagon-like peptides
Peptide hormones
ROSE-010
exendin(9-39) amide
Fysiologi
Physiology

Publikations- och innehållstyp

ovr (ämneskategori)
vet (ämneskategori)

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