Discovery, characterization, and clinical development of the glucagon-like peptides

被引:299
作者
Drucker, Daniel J. [1 ]
Habener, Joel F. [2 ]
Holst, Jens Juul [3 ]
机构
[1] Univ Toronto, Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada
[2] Harvard Univ, Massachusetts Gen Hosp, Lab Mol Endocrinol, Boston, MA USA
[3] Univ Copenhagen, Dept Biomed Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark
关键词
GASTRIC-INHIBITORY POLYPEPTIDE; GLP-1 RECEPTOR ACTIVATION; BETA-CELL FUNCTION; PROGLUCAGON GENE-EXPRESSION; GUT GLUCAGON; CARDIOVASCULAR OUTCOMES; PREPROGLUCAGON CONTAINS; GLYCEMIC CONTROL; SMALL-INTESTINE; MICE BEARING;
D O I
10.1172/JCI97233
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
The discovery, characterization, and clinical development of glucagon-likepeptide- 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.
引用
收藏
页码:4217 / 4227
页数:11
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