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Am J Physiol Gastrointest Liver Physiol 292: G1474-G1482, 2007. First published February 22, 2007; doi:10.1152/ajpgi.00562.2006
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NEUROREGULATION AND MOTILITY

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

S. Wan,1,2 F. H. Coleman,1 and R. A. Travagli1

1Department of Neuroscience, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana; and 2Department of Physiology, Wuhan University School of Basic Medical Science, Wuhan, People's Republic of China

Submitted 11 December 2006 ; accepted in final form 12 February 2007

Glucagon-like peptide-1 (GLP-1) increases pancreatic insulin secretion via a direct action on pancreatic beta-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).

brain stem; electrophysiology; vagus; pancreas



Address for reprint requests and other correspondence: R. A. Travagli, Dept. of Neuroscience, Pennington Biomedical Research Center, Louisiana State Univ. System, Baton Rouge, LA 70808 (e-mail: alberto.travagli{at}pbrc.edu)




This article has been cited by other articles:


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J. Neurosci.Home page
S. Wan, K. N. Browning, F. H. Coleman, G. Sutton, H. Zheng, A. Butler, H.-R. Berthoud, and R. A. Travagli
Presynaptic Melanocortin-4 Receptors on Vagal Afferent Fibers Modulate the Excitability of Rat Nucleus Tractus Solitarius Neurons
J. Neurosci., May 7, 2008; 28(19): 4957 - 4966.
[Abstract] [Full Text] [PDF]


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Am. J. Physiol. Gastrointest. Liver Physiol.Home page
S. Wan, F. H. Coleman, and R. A. Travagli
Cholecystokinin-8s excites identified rat pancreatic-projecting vagal motoneurons
Am J Physiol Gastrointest Liver Physiol, August 1, 2007; 293(2): G484 - G492.
[Abstract] [Full Text] [PDF]




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