Effect of guanylate cyclase-C activity on energy and glucose homeostasis

  1. Randy J. Seeley1
  1. 1Metabolic Diseases Institute, University of Cincinnati, Cincinnati, OH, 45237
  2. 2School of Psychology, University of New South Wales, UNSW Sydney, NSW, Australia, 2052
  3. 3Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45220
  1. Corresponding Author: Denovan P. Begg, Email: d.begg{at}, dpbegg{at}


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. Here, we tested CNS 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 centrally mediated by central GC-C receptors.

  • Received January 29, 2014.
  • Accepted May 29, 2014.

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