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In vitro, KBP-042 demonstrated superior binding affinity and activation of amylin and calcitonin receptors, and ex vivo, KBP-042 exerted inhibitory action on stimulated insulin and glucagon release from isolated islets. In vivo, KBP-042 induced a superior and pronounced reduction in food intake in conjunction with a sustained pair-fed corrected weight loss in DIO rats. Concomitantly, KBP-042 improved glucose homeostasis and reduced hyperinsulinemia and hyperleptinemia in conjunction with enhanced insulin sensitivity. In ZDF rats, KBP-042 induced a superior attenuation of diabetic hyperglycemia and alleviated impaired glucose and insulin tolerance. Concomitantly, KBP-042 preserved insulinotropic and induced glucagonostatic action, ultimately preserving pancreatic insulin and glucagon content. In conclusion, oral KBP-042 is a novel DACRA, which exerts antiobesity and antidiabetic efficacy by dual modulation of insulin sensitivity and directly decelerating stress on the pancreatic \u03b1- and \u03b2-cells. These results could provide the basis for oral KBP-042 as a novel therapeutic agent in type 2 diabetes.<\/jats:p>","DOI":"10.1152\/ajpendo.00121.2014","type":"journal-article","created":{"date-parts":[[2014,5,7]],"date-time":"2014-05-07T06:57:25Z","timestamp":1399445845000},"page":"E24-E33","source":"Crossref","is-referenced-by-count":65,"title":["A novel oral dual amylin and calcitonin receptor agonist (KBP-042) exerts antiobesity and antidiabetic effects in rats"],"prefix":"10.1152","volume":"307","author":[{"given":"Kim V.","family":"Andreassen","sequence":"first","affiliation":[{"name":"Nordic Bioscience, Herlev, Denmark; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Feigh","sequence":"additional","affiliation":[{"name":"Nordic Bioscience, Herlev, Denmark; and"},{"name":"Diabetes Research Centre, Department of Endocrinology, University of Southern Denmark, Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara 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