Glucagon-Like Peptide-1 Inhibits Prandial Gastrointestinal Motility Through Myenteric Neuronal Mechanisms in Humans

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Glucagon-Like Peptide-1 Inhibits Prandial Gastrointestinal Motility Through Myenteric Neuronal Mechanisms in Humans. / Halim, Md. Abdul; Degerblad, Marie; Sundbom, Magnus; Karlbom, Urban; Holst, Jens Juul; Webb, Dominic-Luc; Hellstrom, Per M.

In: Journal of Clinical Endocrinology & Metabolism, Vol. 103, No. 2, 2018, p. 575-585.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Halim, MA, Degerblad, M, Sundbom, M, Karlbom, U, Holst, JJ, Webb, D-L & Hellstrom, PM 2018, 'Glucagon-Like Peptide-1 Inhibits Prandial Gastrointestinal Motility Through Myenteric Neuronal Mechanisms in Humans', Journal of Clinical Endocrinology & Metabolism, vol. 103, no. 2, pp. 575-585. https://doi.org/10.1210/jc.2017-02006

APA

Halim, M. A., Degerblad, M., Sundbom, M., Karlbom, U., Holst, J. J., Webb, D-L., & Hellstrom, P. M. (2018). Glucagon-Like Peptide-1 Inhibits Prandial Gastrointestinal Motility Through Myenteric Neuronal Mechanisms in Humans. Journal of Clinical Endocrinology & Metabolism, 103(2), 575-585. https://doi.org/10.1210/jc.2017-02006

Vancouver

Halim MA, Degerblad M, Sundbom M, Karlbom U, Holst JJ, Webb D-L et al. Glucagon-Like Peptide-1 Inhibits Prandial Gastrointestinal Motility Through Myenteric Neuronal Mechanisms in Humans. Journal of Clinical Endocrinology & Metabolism. 2018;103(2):575-585. https://doi.org/10.1210/jc.2017-02006

Author

Halim, Md. Abdul ; Degerblad, Marie ; Sundbom, Magnus ; Karlbom, Urban ; Holst, Jens Juul ; Webb, Dominic-Luc ; Hellstrom, Per M. / Glucagon-Like Peptide-1 Inhibits Prandial Gastrointestinal Motility Through Myenteric Neuronal Mechanisms in Humans. In: Journal of Clinical Endocrinology & Metabolism. 2018 ; Vol. 103, No. 2. pp. 575-585.

Bibtex

@article{88453a6648ce44419105428d3c8ea658,
title = "Glucagon-Like Peptide-1 Inhibits Prandial Gastrointestinal Motility Through Myenteric Neuronal Mechanisms in Humans",
abstract = "Context: Glucagon-like peptide-1 (GLP-1) secretion from L-cells and postprandial inhibition of gastrointestinal motility. Objective: Investigate whether physiological plasma concentrations of GLP-1 inhibit human postprandial motility and determine mechanism of action of GLP-1 and analog ROSE-010 action. Design: Single-blind parallel study. Setting: University hospital laboratory. Participants: Healthy volunteers investigated with antroduodenal manometry. Human gastric and intestinal muscle strips. Interventions: Motility indices (MIs) obtained before and during GLP-1 or saline infusion. Plasma GLP-1 and glucagon-like peptide-2 (GLP-2) measured by radioimmunoassay. Gastrointestinal muscle strips investigated for GLP-1- and ROSE-010-induced relaxation employing GLP-1 and GLP-2 and their receptor localization, and blockers exendin(9-39) amide, L-omega-nitro-monomethylarginine (L-NMMA), 2',5'-dideoxyadenosine (DDA), and tetrodotoxin (TTX) to reveal target mechanism of GLP-1 action. Main Outcome Measures: Postprandial gastrointestinal relaxation by GLP-1. Results: In humans, food intake increased MI to 6.4 +/- 0.3 (antrum), 5.7 +/- 0.4 (duodenum), and 5.9 +/- 0.2 (jejunum). GLP-1 administered intravenously raised plasma GLP-1, but not GLP-2. GLP-1 0.7 pmol/kg/min suppressed corresponding MI to 4.6 +/- 0.2, 4.7 +/- 0.4, and 5.0 +/- 0.2, whereas 1.2 pmol/kg/min suppressed MI to 5.4 +/- 0.2, 4.4 +/- 0.3, and 5.4 +/- 0.3 (P < 0.0001 to 0.005). In vitro, GLP-1 and ROSE-010 prevented contractions by bethanechol and electric field stimulation (P < 0.005 to 0.05). These effects were disinhibited by exendin(9-39) amide, L-NMMA, DDA, or TTX. GLP-1 and GLP-2 were localized to epithelial cells, GLP-1 also at myenteric neurons. GLP-1R and GLP-2R were localized at myenteric neurons but not muscle. Conclusions: GLP-1 and ROSE-010 inhibit postprandial gastrointestinal motility through GLP-1R at myenteric neurons, involving nitrergic and cyclic adenosine monophosphate-dependent mechanisms.",
author = "Halim, {Md. Abdul} and Marie Degerblad and Magnus Sundbom and Urban Karlbom and Holst, {Jens Juul} and Dominic-Luc Webb and Hellstrom, {Per M.}",
year = "2018",
doi = "10.1210/jc.2017-02006",
language = "English",
volume = "103",
pages = "575--585",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "Oxford University Press",
number = "2",

}

RIS

TY - JOUR

T1 - Glucagon-Like Peptide-1 Inhibits Prandial Gastrointestinal Motility Through Myenteric Neuronal Mechanisms in Humans

AU - Halim, Md. Abdul

AU - Degerblad, Marie

AU - Sundbom, Magnus

AU - Karlbom, Urban

AU - Holst, Jens Juul

AU - Webb, Dominic-Luc

AU - Hellstrom, Per M.

PY - 2018

Y1 - 2018

N2 - Context: Glucagon-like peptide-1 (GLP-1) secretion from L-cells and postprandial inhibition of gastrointestinal motility. Objective: Investigate whether physiological plasma concentrations of GLP-1 inhibit human postprandial motility and determine mechanism of action of GLP-1 and analog ROSE-010 action. Design: Single-blind parallel study. Setting: University hospital laboratory. Participants: Healthy volunteers investigated with antroduodenal manometry. Human gastric and intestinal muscle strips. Interventions: Motility indices (MIs) obtained before and during GLP-1 or saline infusion. Plasma GLP-1 and glucagon-like peptide-2 (GLP-2) measured by radioimmunoassay. Gastrointestinal muscle strips investigated for GLP-1- and ROSE-010-induced relaxation employing GLP-1 and GLP-2 and their receptor localization, and blockers exendin(9-39) amide, L-omega-nitro-monomethylarginine (L-NMMA), 2',5'-dideoxyadenosine (DDA), and tetrodotoxin (TTX) to reveal target mechanism of GLP-1 action. Main Outcome Measures: Postprandial gastrointestinal relaxation by GLP-1. Results: In humans, food intake increased MI to 6.4 +/- 0.3 (antrum), 5.7 +/- 0.4 (duodenum), and 5.9 +/- 0.2 (jejunum). GLP-1 administered intravenously raised plasma GLP-1, but not GLP-2. GLP-1 0.7 pmol/kg/min suppressed corresponding MI to 4.6 +/- 0.2, 4.7 +/- 0.4, and 5.0 +/- 0.2, whereas 1.2 pmol/kg/min suppressed MI to 5.4 +/- 0.2, 4.4 +/- 0.3, and 5.4 +/- 0.3 (P < 0.0001 to 0.005). In vitro, GLP-1 and ROSE-010 prevented contractions by bethanechol and electric field stimulation (P < 0.005 to 0.05). These effects were disinhibited by exendin(9-39) amide, L-NMMA, DDA, or TTX. GLP-1 and GLP-2 were localized to epithelial cells, GLP-1 also at myenteric neurons. GLP-1R and GLP-2R were localized at myenteric neurons but not muscle. Conclusions: GLP-1 and ROSE-010 inhibit postprandial gastrointestinal motility through GLP-1R at myenteric neurons, involving nitrergic and cyclic adenosine monophosphate-dependent mechanisms.

AB - Context: Glucagon-like peptide-1 (GLP-1) secretion from L-cells and postprandial inhibition of gastrointestinal motility. Objective: Investigate whether physiological plasma concentrations of GLP-1 inhibit human postprandial motility and determine mechanism of action of GLP-1 and analog ROSE-010 action. Design: Single-blind parallel study. Setting: University hospital laboratory. Participants: Healthy volunteers investigated with antroduodenal manometry. Human gastric and intestinal muscle strips. Interventions: Motility indices (MIs) obtained before and during GLP-1 or saline infusion. Plasma GLP-1 and glucagon-like peptide-2 (GLP-2) measured by radioimmunoassay. Gastrointestinal muscle strips investigated for GLP-1- and ROSE-010-induced relaxation employing GLP-1 and GLP-2 and their receptor localization, and blockers exendin(9-39) amide, L-omega-nitro-monomethylarginine (L-NMMA), 2',5'-dideoxyadenosine (DDA), and tetrodotoxin (TTX) to reveal target mechanism of GLP-1 action. Main Outcome Measures: Postprandial gastrointestinal relaxation by GLP-1. Results: In humans, food intake increased MI to 6.4 +/- 0.3 (antrum), 5.7 +/- 0.4 (duodenum), and 5.9 +/- 0.2 (jejunum). GLP-1 administered intravenously raised plasma GLP-1, but not GLP-2. GLP-1 0.7 pmol/kg/min suppressed corresponding MI to 4.6 +/- 0.2, 4.7 +/- 0.4, and 5.0 +/- 0.2, whereas 1.2 pmol/kg/min suppressed MI to 5.4 +/- 0.2, 4.4 +/- 0.3, and 5.4 +/- 0.3 (P < 0.0001 to 0.005). In vitro, GLP-1 and ROSE-010 prevented contractions by bethanechol and electric field stimulation (P < 0.005 to 0.05). These effects were disinhibited by exendin(9-39) amide, L-NMMA, DDA, or TTX. GLP-1 and GLP-2 were localized to epithelial cells, GLP-1 also at myenteric neurons. GLP-1R and GLP-2R were localized at myenteric neurons but not muscle. Conclusions: GLP-1 and ROSE-010 inhibit postprandial gastrointestinal motility through GLP-1R at myenteric neurons, involving nitrergic and cyclic adenosine monophosphate-dependent mechanisms.

U2 - 10.1210/jc.2017-02006

DO - 10.1210/jc.2017-02006

M3 - Journal article

C2 - 29177486

VL - 103

SP - 575

EP - 585

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 2

ER -

ID: 216022828