{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:15:26Z","timestamp":1791317726223,"version":"4.3.1"},"reference-count":19,"publisher":"American Physiological Society","issue":"10","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Endocrinology and Metabolism"],"published-print":{"date-parts":[[2016,5,15]]},"abstract":"<jats:p> This study aims to elucidate the mechanism behind the potent weight loss induced by dual amylin and calcitonin receptor agonists (DACRA) through comparison of the novel DACRA KBP-088 with the amylinomimetic davalintide with regard to in vitro receptor pharmacology and in vivo efficacy on food intake and body weight. KBP-088 and davalintide were tested for their ability to activate the amylin and calcitonin receptors as function of dose and time. Two doses of KBP-088 (1.67 and 5.0 \u03bcg\/kg) were compared with similar davalintide doses in high-fat diet (HFD)-fed rats receiving subcutaneous dosing once daily for 62 days. Glucose tolerance was assessed after 3 and 7 wk of treatment. KBP-088 demonstrated activation of amylin and calcitonin receptors and prolonged receptor activation compared with davalintide as well as a potent reduction of acute food intake. KBP-088 transiently reduced food intake and induced and notably sustained a significant \u223c16% vehicle-corrected weight loss without significant weight loss in the calorie-restricted control groups. Additionally, KBP-088 reduced white adipose tissues and adipocyte hypertrophy. Finally, KBP-088 alleviated hyperinsulinemia and improved oral glucose tolerance even with significantly lower insulin levels after 3 and 7 wk of treatment. KBP-088 is a potent amylin and calcitonin receptor agonist with prolonged receptor activation compared with davalintide. Moreover, KBP-088 induced and sustained significant weight loss and reduced overall adiposity and adipocyte hypertrophy in HFD rats. Finally, KBP-088 improved oral glucose tolerance and alleviated hyperinsulinemia, underscoring the potential of KBP-088 as an antiobesity agent with benefits on glucose control. <\/jats:p>","DOI":"10.1152\/ajpendo.00514.2015","type":"journal-article","created":{"date-parts":[[2016,2,23]],"date-time":"2016-02-23T23:48:38Z","timestamp":1456271318000},"page":"E821-E827","source":"Crossref","is-referenced-by-count":47,"title":["KBP-088, a novel DACRA with prolonged receptor activation, is superior to davalintide in terms of efficacy on body weight"],"prefix":"10.1152","volume":"310","author":[{"given":"Sofie","family":"Gydesen","sequence":"first","affiliation":[{"name":"Nordic Bioscience, Herlev, Denmark; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim Vietz","family":"Andreassen","sequence":"additional","affiliation":[{"name":"Nordic Bioscience, Herlev, Denmark; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara Toftegaard","family":"Hjuler","sequence":"additional","affiliation":[{"name":"Nordic Bioscience, Herlev, Denmark; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane Marie","family":"Christensen","sequence":"additional","affiliation":[{"name":"Nordic Bioscience, Herlev, Denmark; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morten Asser","family":"Karsdal","sequence":"additional","affiliation":[{"name":"Nordic Bioscience, Herlev, Denmark; and"},{"name":"KeyBioscience AG, Stans, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Henriksen","sequence":"additional","affiliation":[{"name":"Nordic Bioscience, Herlev, Denmark; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00121.2014"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0092042"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1210\/en.2012-2172"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1124\/pr.115.010629"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2015.05.051"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/nature05482"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00297.2007"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1111\/j.1463-1326.2011.01465.x"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/ijo.2009.238"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1210\/en.2006-0393"},{"key":"B12","first-page":"203","volume":"2","author":"Ryan G","year":"2009","journal-title":"Drug Des Devel Ther"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1172\/JCI105705"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/nri1937"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2005.03.002"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1210\/en.2010-0590"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.2174\/1381612013397357"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.physbeh.2010.04.012"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/S1054-3589(05)52006-4"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1007\/BF00401833"}],"container-title":["American Journal of Physiology-Endocrinology and Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpendo.00514.2015","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T16:39:05Z","timestamp":1567960745000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpendo.00514.2015"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,5,15]]},"references-count":19,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2016,5,15]]}},"alternative-id":["10.1152\/ajpendo.00514.2015"],"URL":"https:\/\/doi.org\/10.1152\/ajpendo.00514.2015","relation":{},"ISSN":["0193-1849","1522-1555"],"issn-type":[{"value":"0193-1849","type":"print"},{"value":"1522-1555","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,5,15]]}}}