Building the Glucagon-Like Peptide-1 Receptor Brick by Brick: Revisiting a 1993 Diabetes Classic by Thorens et al.

Diabetes

Oxford Centre for Diabetes, Endocrinology, and Metabolism (OCDEM), National Institute for Health and Care Research Oxford Biomedical Research Centre, Radcliffe Department of Medicine, Churchill Hospital, University of Oxford, Oxford, U.K.

Published: July 2024

The glucagon-like peptide-1 receptor (GLP-1R) is a class B G protein-coupled receptor involved in the regulation of blood glucose levels and food intake. Stabilized agonists targeting GLP-1R are used in the treatment of type 2 diabetes and have recently become a breakthrough obesity therapy. Here, we revisit a classic article in Diabetes by Thorens et al. that described the cloning, sequencing, and functional expression of the human GLP-1R. The article also demonstrated that exendin4(1-39) was a full agonist of the human GLP-1R whereas exendin4(9-39) was a full antagonist. We discuss how the knowledge imparted by these studies has gone on to inform multiple strands of GLP-1R biology over the past three decades, including pharmacology, signaling, human genetics, structural biology, and chemical biology.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11189827PMC
http://dx.doi.org/10.2337/dbi24-0025DOI Listing

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