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1 Neuroscience, Pennington Biomedical Research Center-LSU, Baton Rouge, Louisiana, United States; Physiology, Wuhan University School of Basic Medical Science, Wuhan, China
2 Neuroscience, Pennington Biomedical Research Center-LSU, Baton Rouge, Louisiana, United States
* To whom correspondence should be addressed. E-mail: alberto.travagli{at}pbrc.edu.
Glucagon-like peptide-1 (GLP-1) increases pancreatic insulin secretion via a direct action on pancreatic
-cells. A high density of GLP-1 containing neurons and receptors is also present in brainstem 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 TTX (1µM) suggesting both pre- and post-synaptic sites of action. Indeed, the GLP-1 effects were mediated by actions on gKs, 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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