New developments in the prospects for GLP-1 therapy.
New developments in the prospects for GLP-1 therapy.
复制标题
GLP-1治疗前景的新进展。
DOI：
10.1111/bph.15788
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发表时间：
2022
影响因子：
7.3
通讯作者：
Trapp S
中科院分区：
文献类型：
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作者：
Trapp S
胰高血糖素样肽-1（GLP-1）受体激动剂Semaglutide最近已被证实为临床使用中最有效的减肥药物（Wilding et al.，2021），其突出了在临床开发不起眼的30个氨基酸肠促胰岛素激素GLP-1方面的重大成功。肠促胰岛素是由消化系统产生的激素，其通过刺激胰腺激素，特别是胰岛素的分泌来促进血浆中葡萄糖浓度的降低。肠促胰岛素效应描述了口服摄入葡萄糖后，与直接将葡萄糖输注到血流中诱导的胰岛素释放相比，更有效地刺激胰岛素释放。因此，在20世纪80年代被鉴定为肠促胰岛素后，对GLP-1的早期兴趣集中在这种作用上，并导致开发了耐降解GLP-1受体激动剂，如艾塞那肽、利拉鲁肽、阿必鲁肽等，目前已成功用于临床作为2型糖尿病的二线治疗。从那时起，通过这些激动剂的临床使用以及密集的临床前研究收集的证据大大增加了我们对GLP-1生理学的理解，并刺激了新型GLP-1受体激动剂的开发。
The glucagon-like peptide-1 (GLP-1) receptor agonist, semaglutide, has recently been confirmed as the most efficacious weight-loss drug in clinical use (Wilding et al., 2021), which highlights a major success in the clinical exploitation of the humble 30 amino acid incretin hormone, GLP-1.An incretin is a hormone, produced by the digestive system, that promotes the lowering of the concentration of glucose in the plasma by stimulating the secretion of pancreatic hormones, particularly insulin. The incretin effect describes the more effective stimulation of insulin release following oral ingestion of glucose, by comparison with that induced by infusion of glucose directly into the bloodstream. Thus, after its identification as an incretin in the 1980s, early interest in GLP-1 focussed on this effect and led to the development of degradation-resistant GLP-1 receptor agonists, such as exenatide, liraglutide, albiglutide and others, which are now used successfully in the clinic as second-line treatments for type 2 diabetes mellitus. Since then, evidence gathered through clinical use of these agonists, as well as intense preclinical research, has increased our understanding of the physiology of GLP-1 appreciably and stimulated the development of novel GLP-1 receptor agonists.