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Cholecystokinin regulates satiation independently of the abdominal vagal nerve in a pig model of total subdiaphragmatic vagotomy

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Author: Ripken, D. · Wielen, N. van der · Meulen, J. van der · Schuurman, T. · Witkamp, R.F. · Hendriks, H.F.J. · Koopmans, S.J.
Type:article
Date:2015
Source:Physiology and Behavior, 139, 167-176
Identifier: 520239
doi: doi:10.1016/j.physbeh.2014.11.031
Keywords: Biology · Cholecystokinin · Devazepide · Exendin (9-39) · Food intake regulation · Glucagon-like peptide 1 · Vagal nerve · Cholecystokinin · Cholecystokinin A receptor · Glucagon like peptide 1 · Glucagon like peptide 1 receptor · Glucose · Insulin · Paracetamol · Abdominal vagal nerve · Animal experiment · Animal model · Animal tissue · Autopsy · Cholecystokinin blood level · Controlled study · Drug absorption · Drug blood level · Fluid intake · Food intake · Glucose blood level · Hormonal regulation · Hormone response · Insulin blood level · Intestine motility · Male · Maximum plasma concentration · Nonhuman · Postprandial state · Patiety · Sham procedure · Stomach absorption · Stomach content · Stomach emptying · Subdiaphragmatic vagotomy · Time to maximum plasma concentration · Vagotomy · Vagus nerve · Weight gain · Biomedical Innovation · Healthy Living · Life · MSB - Microbiology and Systems Biology · ELSS - Earth, Life and Social Sciences

Abstract

The vagal nerve and gut hormones CCK and GLP-1 play important roles in the control of food intake. However, it is not clear to what extent CCK and GLP-1 increase satiation by stimulating receptors located on abdominal vagal nerve endings or via receptors located elsewhere. This study aimed to further explore the relative contribution of the abdominal vagal nerve in mediating the satiating effects of endogenous CCK and GLP-1. Total subdiaphragmatic vagotomy or sham operation was combined with administration of CCK1 and GLP-1 receptor antagonists devazepide and exendin (9-39) in 12 pigs, applying an unbalanced Latin Square within-subject design. Furthermore, effects of vagotomy on preprandial and postprandial acetaminophen absorption, glucose, insulin, GLP-1 and CCK plasma concentrations were investigated.Ad libitum liquid meal intake (mean±SEM) was similar in sham and vagotomized pigs (4180±435 and 3760±810g/meal). Intake increased by about 20% after blockade of CCK1 receptors, independently of the abdominal vagal nerve. Food intake did not increase after blockade of GLP-1 receptors. Blockade of CCK1 and GLP-1 receptors increased circulating CCK and GLP-1 concentrations in sham pigs only, suggesting the existence of a vagal reflex mechanism in the regulation of plasma CCK1 and GLP-1 concentrations. Vagotomy decreased acetaminophen absorption and changed glucose, insulin, CCK and GLP-1 concentrations indicating a delay in gastric emptying. Our data show that at liquid feeding, satiation is decreased effectively by pharmacological blockade of CCK1 receptors. We conclude that regulation of liquid meal intake appears to be primarily regulated by CCK1 receptors not located on abdominal vagal nerve endings. Chemicals/CAS: cholecystokinin, 9011-97-6, 93443-27-7; devazepide, 103420-77-5; glucagon like peptide 1, 89750-14-1; glucose, 50-99-7, 84778-64-3; insulin, 9004-10-8; paracetamol, 103-90-2