Effect of Guanylate Cyclase-C Activity on Energy and Glucose

Uroguanylin is a gastrointestinal hormone primarily in-volved in fluid and electrolyte handling. It has recently been reported that prouroguanylin, secreted postpran-dially, 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 phenotypedmice 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 intoler-ance. Our data indicate that the modest effects of uroguanylin on energy and glucose homeostasis are no