胰淀素
赛马鲁肽
效力
牛蛙
内科学
内分泌学
医学
减肥
饮食性肥胖
药理学
受体
肥胖
胰岛素
化学
糖尿病
2型糖尿病
生物化学
体外
胰岛素抵抗
小岛
利拉鲁肽
作者
Xiao Sun,Dawei Yang,Y. Li,Jingjing Shi,Xiaolong Zhang,Tingzhuang Yi
出处
期刊:Peptides
[Elsevier]
日期:2024-07-01
卷期号:177: 171203-171203
标识
DOI:10.1016/j.peptides.2024.171203
摘要
This study assesses the efficacy of an innovative therapeutic approach that combines GLP-1 and amylin analogues for weight reduction. Focusing on GLP-1 analogues from bullfrog (Rana catesbeiana), we designed ten bGLP-1 analogues with various modifications. Among them, bGLP-10 showed high potency in binding and activating GLP-1 receptors, with superior albumin affinity. In diet-induced obesity (DIO) mice fed a high-fat diet, bGLP-10 demonstrated significant superiority over semaglutide in reducing blood sugar and food intake at a dose of 10 nmol/kg (P < 0.001). Notably, in a chronic study involving DIO mice, the combination of bGLP-10 with the amylin analogue cagrilintide led to a more substantial weight loss (-38.4%, P < 0.001) compared to either the semaglutide-cagrilintide combination (-23.0%) or cagrilintide (-5.7%), bGLP-10 (-16.1%), and semaglutide (-10.9%) alone. Furthermore, the bGLP-10 and cagrilintide combination exhibited superior glucose control and liver lipid management compared to the semaglutide-cagrilintide combination (P < 0.001). These results highlight bGLP-10's potential in GLP-1 and amylin-based therapies and suggest exploring more GLP-1 analogues from natural sources for anti-obesity and anti-diabetic treatments.
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