A GLP‐1/glucagon (GCG)/CCK2 receptors tri‐agonist provides new therapy for obesity and diabetes

• DOI: 10.1111/bph.15860
• Publication Date: 2022-04-29T05:14:53Z
• Authors: Songfeng Zhao; Zhiming Yan; Yue Du; Zeyun Li; Chunli Tang; Lin Jing; Lidan Sun; Qimeng Yang; Xueling Tang; Yongliang Yuan; Jing Han; Neng Jiang
• Keywords: Cholecystokinin B receptor

Glucagon-like peptide-1 (GLP-1) and glucagon (GCG) receptor dual agonist have promising therapeutic effects in the treatment of obesity diabetes. Moreover, GLP-1 cholecystokinin 2 (CCK2 ) agonists been shown to restore pancreas function improve glycaemic control preclinical studies. We describe, for first time, beneficial GLP-1/glucagon GLP-1/CCK2 agonists, which can be integrated into one peptide, resulting significant anti-diabetes anti-obesity effectiveness.The vitro potency this novel peptide Xenopus (x) GLP-1/GCG/CCK2 tri-agonist (xGLP/GCG/gastrin) against GLP-1, GCG, CCK1 CCK2 receptors was determined on cells expressing corresponding by cAMP accumulation or ERK1/2 phosphorylation assays. The vivo xGLP/GCG/gastrin were studied both db/db diet induced (DIO) mice.xGLP/GCG/gastrin a potent selective GCG tri-agonist. In DIO mice, metabolic benefits xGLP-1/GCG/gastrin, such as reduction body weight hepatic lipid contents significantly better than those ZP3022 (GLP-1/CCK-2 agonist) liraglutide. short-term study had considerable effects, increasing islet numbers, areas insulin content. long-term using xGLP-1/GCG/gastrin showed sustained improvement glucose tolerance compared with that liraglutide, ZP3022, cotadutide (GLP-1/GCG xGLP/GCG-15.These results demonstrate potential