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Novikoff, A. ; Müller, T.D.

The molecular pharmacology of glucagon agonists in diabetes and obesity.

Peptides 165:171003 (2023)
Publ. Version/Full Text DOI PMC
Open Access Gold (Paid Option)
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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Publication type Article: Journal article
Document type Review
Corresponding Author
Keywords 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
ISSN (print) / ISBN 0196-9781
e-ISSN 1873-5169
Journal Peptides
Quellenangaben Volume: 165, Issue: , Pages: , Article Number: 171003 Supplement: ,
Publisher Elsevier
Publishing Place New York, NY
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Obesity (IDO)
Grants German Center for Diabetes Research (DZD e.V.)
German Research Foundation
European Research Council (ERC) within the ERC CoG Trusted