Drucker Daniel J, Habener Joel F, Holst Jens Juul
Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.
Laboratory of Molecular Endocrinology, Massachusetts General Hospital, Harvard University, Boston, Massachusetts, USA.
J Clin Invest. 2017 Dec 1;127(12):4217-4227. doi: 10.1172/JCI97233.
The discovery, characterization, and clinical development of glucagon-like-peptide-1 (GLP-1) spans more than 30 years and includes contributions from multiple investigators, science recognized by the 2017 Harrington Award Prize for Innovation in Medicine. Herein, we provide perspectives on the historical events and key experimental findings establishing the biology of GLP-1 as an insulin-stimulating glucoregulatory hormone. Important attributes of GLP-1 action and enteroendocrine science are reviewed, with emphasis on mechanistic advances and clinical proof-of-concept studies. The discovery that GLP-2 promotes mucosal growth in the intestine is described, and key findings from both preclinical studies and the GLP-2 clinical development program for short bowel syndrome (SBS) are reviewed. Finally, we summarize recent progress in GLP biology, highlighting emerging concepts and scientific insights with translational relevance.
胰高血糖素样肽-1(GLP-1)的发现、特性鉴定及临床开发历经30多年,涉及多位研究者的贡献,这一科学成果荣获2017年哈林顿医学创新奖。在此,我们阐述了确立GLP-1作为胰岛素刺激型血糖调节激素生物学特性的历史事件和关键实验发现。回顾了GLP-1作用及肠内分泌科学的重要特性,重点介绍了机制进展和临床概念验证研究。描述了GLP-2促进肠道黏膜生长的发现,并回顾了临床前研究和短肠综合征(SBS)的GLP-2临床开发项目的关键发现。最后,我们总结了GLP生物学的最新进展,突出了具有转化相关性的新兴概念和科学见解。