title: Effect of guanylate cyclase-C activity on energy and glucose homeostasis.
abstract: Uroguanylin is a gastrointestinal hormone primarily involved in fluid and electrolyte handling. It has recently been reported that prouroguanylin, secreted postprandially, is converted to uroguanylin in the brain and activates the receptor guanylate cyclase-C (GC-C) to reduce food intake and prevent obesity. We tested central nervous system administration of two GC-C agonists and found no significant reduction of food intake. We also carefully phenotyped mice lacking the GC-C receptor and found them to have normal body weight, adiposity, and glucose tolerance. Interestingly, uroguanylin knockout mice had a small but significant increase in body weight and adiposity that was accompanied by glucose intolerance. Our data indicate that the modest effects of uroguanylin on energy and glucose homeostasis are not mediated by central GC-C receptors.
authors.affiliation: Metabolic Diseases Institute, University of Cincinnati, Cincinnati, OH School of Psychology, University of New South Wales, Sydney, New South Wales, Australia d.begg@unsw.edu.au.
authors.forename: Denovan P
authors.initials: DP
authors.lastname: Begg
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
authors.forename: Kris A
authors.initials: KA
authors.lastname: Steinbrecher
authors.affiliation: Metabolic Diseases Institute, University of Cincinnati, Cincinnati, OH.
authors.forename: Joram D
authors.initials: JD
authors.lastname: Mul
authors.affiliation: Metabolic Diseases Institute, University of Cincinnati, Cincinnati, OH.
authors.forename: Adam P
authors.initials: AP
authors.lastname: Chambers
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
authors.forename: Rohit
authors.initials: R
authors.lastname: Kohli
authors.affiliation: Metabolic Diseases Institute, University of Cincinnati, Cincinnati, OH.
authors.forename: April
authors.initials: A
authors.lastname: Haller
authors.affiliation: Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
authors.forename: Mitchell B
authors.initials: MB
authors.lastname: Cohen
authors.affiliation: Metabolic Diseases Institute, University of Cincinnati, Cincinnati, OH.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Woods
authors.affiliation: Metabolic Diseases Institute, University of Cincinnati, Cincinnati, OH.
authors.forename: Randy J
authors.initials: RJ
authors.lastname: Seeley
mesh_terms: D000818:Animals; D006152:Cyclic GMP / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D006162:Guanylate Cyclase / Q000378:metabolism*; D008297:Male; D051379:Mice; D045265:Natriuretic Peptides / Q000494:pharmacology; D051381:Rats; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled / Q000378:metabolism; D018000:Receptors, Peptide / Q000378:metabolism
chemical_list: D045265:Natriuretic Peptides; D018000:Receptors, Peptide; C084362:uroguanylin; D006162:Guanylate Cyclase; C000613655:Gucy2c protein, mouse; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled; D006152:Cyclic GMP; D005947:Glucose