Glucagon-like peptide-1 excites pancreas-projecting preganglionic vagal motoneurons

S. Wan, F. H. Coleman, R. A. Travagli

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Glucagon-like peptide-1 (GLP-1) increases pancreatic insulin secretion via a direct action on pancreatic β-cells. A high density of GLP-1-containing neurons and receptors is also present in brain stem vagal circuits; therefore, the aims of the present study were to investigate 1) whether identified pancreas-projecting neurons of the dorsal motor nucleus of the vagus (DMV) respond to exogenously applied GLP-1, 2) the mechanism(s) of action of GLP-1, and 3) whether the GLP-1-responsive neurons (putative modulators of endocrine secretion) could be distinguished from DMV neurons responsive to peptides that modulate pancreatic exocrine secretion, specifically pancreatic polypeptide (PP). Whole cell recordings were made from identified pancreas-projecting DMV neurons. Perfusion with GLP-1 induced a concentration-dependent depolarization in ∼50% of pancreas-projecting DMV neurons. The GLP-1 effects were mimicked by exendin-4 and antagonized by exendin-(9 -39). In ∼60% of the responsive neurons, the GLP-1-induced depolarization was reduced by tetrodotoxin (1 μM), suggesting both pre- and postsynaptic sites of action. Indeed, the GLP-1 effects were mediated by actions on potassium currents, GABA-induced currents, or both. Importantly, neurons excited by GLP-1 were unresponsive to PP and vice versa. These data indicate that 1) GLP-1 may act on DMV neurons to control pancreatic endocrine secretion, 2) the effects of GLP-1 on pancreas-projecting DMV neurons are mediated both via a direct excitation of their membrane as well as via an effect on local circuits, and 3) the GLP-1-responsive neurons (i.e., putative endocrine secretion-controlling neurons) could be distinguished from neurons responsive to PP (i.e., putative exocrine secretion-controlling neurons).

Original languageEnglish (US)
Pages (from-to)G1474-G1482
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume292
Issue number6
DOIs
StatePublished - Jun 1 2007

Fingerprint

Glucagon-Like Peptide 1
Motor Neurons
Pancreas
Neurons
Pancreatic Polypeptide
Glucagon-Like Peptide 2
Tetrodotoxin
Patch-Clamp Techniques
gamma-Aminobutyric Acid
Brain Stem
Potassium

All Science Journal Classification (ASJC) codes

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Cite this

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title = "Glucagon-like peptide-1 excites pancreas-projecting preganglionic vagal motoneurons",
abstract = "Glucagon-like peptide-1 (GLP-1) increases pancreatic insulin secretion via a direct action on pancreatic β-cells. A high density of GLP-1-containing neurons and receptors is also present in brain stem vagal circuits; therefore, the aims of the present study were to investigate 1) whether identified pancreas-projecting neurons of the dorsal motor nucleus of the vagus (DMV) respond to exogenously applied GLP-1, 2) the mechanism(s) of action of GLP-1, and 3) whether the GLP-1-responsive neurons (putative modulators of endocrine secretion) could be distinguished from DMV neurons responsive to peptides that modulate pancreatic exocrine secretion, specifically pancreatic polypeptide (PP). Whole cell recordings were made from identified pancreas-projecting DMV neurons. Perfusion with GLP-1 induced a concentration-dependent depolarization in ∼50{\%} of pancreas-projecting DMV neurons. The GLP-1 effects were mimicked by exendin-4 and antagonized by exendin-(9 -39). In ∼60{\%} of the responsive neurons, the GLP-1-induced depolarization was reduced by tetrodotoxin (1 μM), suggesting both pre- and postsynaptic sites of action. Indeed, the GLP-1 effects were mediated by actions on potassium currents, GABA-induced currents, or both. Importantly, neurons excited by GLP-1 were unresponsive to PP and vice versa. These data indicate that 1) GLP-1 may act on DMV neurons to control pancreatic endocrine secretion, 2) the effects of GLP-1 on pancreas-projecting DMV neurons are mediated both via a direct excitation of their membrane as well as via an effect on local circuits, and 3) the GLP-1-responsive neurons (i.e., putative endocrine secretion-controlling neurons) could be distinguished from neurons responsive to PP (i.e., putative exocrine secretion-controlling neurons).",
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Glucagon-like peptide-1 excites pancreas-projecting preganglionic vagal motoneurons. / Wan, S.; Coleman, F. H.; Travagli, R. A.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 292, No. 6, 01.06.2007, p. G1474-G1482.

Research output: Contribution to journalArticle

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AB - Glucagon-like peptide-1 (GLP-1) increases pancreatic insulin secretion via a direct action on pancreatic β-cells. A high density of GLP-1-containing neurons and receptors is also present in brain stem vagal circuits; therefore, the aims of the present study were to investigate 1) whether identified pancreas-projecting neurons of the dorsal motor nucleus of the vagus (DMV) respond to exogenously applied GLP-1, 2) the mechanism(s) of action of GLP-1, and 3) whether the GLP-1-responsive neurons (putative modulators of endocrine secretion) could be distinguished from DMV neurons responsive to peptides that modulate pancreatic exocrine secretion, specifically pancreatic polypeptide (PP). Whole cell recordings were made from identified pancreas-projecting DMV neurons. Perfusion with GLP-1 induced a concentration-dependent depolarization in ∼50% of pancreas-projecting DMV neurons. The GLP-1 effects were mimicked by exendin-4 and antagonized by exendin-(9 -39). In ∼60% of the responsive neurons, the GLP-1-induced depolarization was reduced by tetrodotoxin (1 μM), suggesting both pre- and postsynaptic sites of action. Indeed, the GLP-1 effects were mediated by actions on potassium currents, GABA-induced currents, or both. Importantly, neurons excited by GLP-1 were unresponsive to PP and vice versa. These data indicate that 1) GLP-1 may act on DMV neurons to control pancreatic endocrine secretion, 2) the effects of GLP-1 on pancreas-projecting DMV neurons are mediated both via a direct excitation of their membrane as well as via an effect on local circuits, and 3) the GLP-1-responsive neurons (i.e., putative endocrine secretion-controlling neurons) could be distinguished from neurons responsive to PP (i.e., putative exocrine secretion-controlling neurons).

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