Begg Denovan P, Steinbrecher Kris A, Mul Joram D, Chambers Adam P, Kohli Rohit, Haller April, Cohen Mitchell B, Woods Stephen C, Seeley Randy J
Metabolic Diseases Institute, University of Cincinnati, Cincinnati, OH School of Psychology, University of New South Wales, Sydney, New South Wales, Australia
Division of Gastroenterology, Hepatology, and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
Diabetes. 2014 Nov;63(11):3798-804. doi: 10.2337/db14-0160. Epub 2014 Jun 4.
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.
尿鸟苷素是一种主要参与体液和电解质调节的胃肠激素。最近有报道称，餐后分泌的前尿鸟苷素在大脑中转化为尿鸟苷素，并激活受体鸟苷酸环化酶-C（GC-C）以减少食物摄入量并预防肥胖。我们测试了两种GC-C激动剂的中枢神经系统给药情况，发现食物摄入量没有显著减少。我们还仔细对缺乏GC-C受体的小鼠进行了表型分析，发现它们的体重、肥胖程度和葡萄糖耐量均正常。有趣的是，尿鸟苷素基因敲除小鼠的体重和肥胖程度有小幅但显著的增加，并伴有葡萄糖不耐受。我们的数据表明，尿鸟苷素对能量和葡萄糖稳态的适度影响并非由中枢GC-C受体介导。
