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Novikoff, A. ; Müller, T.D.

The molecular pharmacology of glucagon agonists in diabetes and obesity.

Peptides 165:171003 (2023)
Verlagsversion DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
Within recent decades glucagon receptor (GcgR) agonism has drawn attention as a therapeutic tool for the treatment of type 2 diabetes and obesity. In both mice and humans, glucagon administration enhances energy expenditure and suppresses food intake suggesting a promising metabolic utility. Therefore synthetic optimization of glucagon-based pharmacology to further resolve the physiological and cellular underpinnings mediating these effects has advanced. Chemical modifications to the glucagon sequence have allowed for greater peptide solubility, stability, circulating half-life, and understanding of the structure-function potential behind partial and "super"-agonists. The knowledge gained from such modifications has provided a basis for the development of long-acting glucagon analogues, chimeric unimolecular dual- and tri-agonists, and novel strategies for nuclear hormone targeting into glucagon receptor-expressing tissues. In this review, we summarize the developments leading toward the current advanced state of glucagon-based pharmacology, while highlighting the associated biological and therapeutic effects in the context of diabetes and obesity.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Review
Schlagwörter Biased Agonism ; Diabetes ; Dual-agonists ; Glucagon ; Obesity ; Pharmacology ; Tri-agonists; Bioactive Enteroglucagon Oxyntomodulin; Receptor Antagonist Ly2409021; Hepatic Glucose-production; Reduces Food-intake; Body-weight Gain; Blood-glucose; Energy-expenditure; Insulin-secretion; Amino-acids; Cyclic-amp
Sprache englisch
Veröffentlichungsjahr 2023
HGF-Berichtsjahr 2023
ISSN (print) / ISBN 0196-9781
e-ISSN 1873-5169
Zeitschrift Peptides
Quellenangaben Band: 165, Heft: , Seiten: , Artikelnummer: 171003 Supplement: ,
Verlag Elsevier
Verlagsort New York, NY
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes and Obesity (IDO)
POF Topic(s) 90000 - German Center for Diabetes Research
30201 - Metabolic Health
Forschungsfeld(er) Helmholtz Diabetes Center
PSP-Element(e) G-501900-221
G-502200-001
Förderungen German Center for Diabetes Research (DZD e.V.)
German Research Foundation
European Research Council (ERC) within the ERC CoG Trusted
DOI 10.1016/j.peptides.2023.171003
WOS ID 000984672800001
Scopus ID 85153503252
PubMed ID 36997003
Erfassungsdatum 2023-10-06
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