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Discovery, characterization, and clinical development of the glucagon-like peptides
Daniel J. Drucker, … , Joel F. Habener, Jens Juul Holst
Daniel J. Drucker, … , Joel F. Habener, Jens Juul Holst
Published December 1, 2017
Citation Information: J Clin Invest. 2017;127(12):4217-4227. https://doi.org/10.1172/JCI97233.
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Harrington Prize Essay Endocrinology Gastroenterology

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

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Abstract

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.

Authors

Daniel J. Drucker, Joel F. Habener, Jens Juul Holst

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Figure 2

Structure and processing of anglerfish and human proglucagon.

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Structure and processing of anglerfish and human proglucagon.
Representa...
Representation of the structures of proglucagon cDNAs from Anglerfish (A) and Human (B), with tissue-specific liberation of individual proglucagon-derived peptides in pancreas or intestine. PC1, prohormone convertase 1; PC2, prohormone convertase 2; MPGF, major proglucagon fragment. Arrows in A represent sites of cleave by prohormone convertase enzymes.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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