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

TY - JOUR

T1 - Discovery, characterization, and clinical development of the glucagon-like peptides

AU - Drucker, Daniel J

AU - Habener, Joel F

AU - Holst, Jens Juul

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

AB - 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.

KW - Animals

KW - Diabetes Mellitus, Type 2

KW - Drug Discovery

KW - Glucagon-Like Peptide 1

KW - Glucagon-Like Peptide 2

KW - Glucagon-Like Peptide-1 Receptor

KW - Humans

KW - Short Bowel Syndrome

KW - Structure-Activity Relationship

KW - Journal Article

KW - Review

U2 - 10.1172/JCI97233

DO - 10.1172/JCI97233

M3 - Review

C2 - 29202475

SN - 0021-9738

VL - 127

SP - 4217

EP - 4227

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

IS - 12

ER -