Publication: Targeting GLP-1 receptor trafficking to improve agonist efficacy
2
Issued Date
2018-12-01
Resource Type
ISSN
20411723
Other identifier(s)
2-s2.0-85046005577
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Mahidol University
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SCOPUS
Bibliographic Citation
Nature Communications. Vol.9, No.1 (2018)
Suggested Citation
Ben Jones, Teresa Buenaventura, Nisha Kanda, Pauline Chabosseau, Bryn M. Owen, Rebecca Scott, Robert Goldin, Napat Angkathunyakul, Ivan R. Corrêa, Domenico Bosco, Paul R. Johnson, Lorenzo Piemonti, Piero Marchetti, A. M.James Shapiro, Blake J. Cochran, Aylin C. Hanyaloglu, Asuka Inoue, Tricia Tan, Guy A. Rutter, Alejandra Tomas, Stephen R. Bloom Targeting GLP-1 receptor trafficking to improve agonist efficacy. Nature Communications. Vol.9, No.1 (2018). doi:10.1038/s41467-018-03941-2 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/44986
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Title
Targeting GLP-1 receptor trafficking to improve agonist efficacy
Author(s)
Ben Jones
Teresa Buenaventura
Nisha Kanda
Pauline Chabosseau
Bryn M. Owen
Rebecca Scott
Robert Goldin
Napat Angkathunyakul
Ivan R. Corrêa
Domenico Bosco
Paul R. Johnson
Lorenzo Piemonti
Piero Marchetti
A. M.James Shapiro
Blake J. Cochran
Aylin C. Hanyaloglu
Asuka Inoue
Tricia Tan
Guy A. Rutter
Alejandra Tomas
Stephen R. Bloom
Teresa Buenaventura
Nisha Kanda
Pauline Chabosseau
Bryn M. Owen
Rebecca Scott
Robert Goldin
Napat Angkathunyakul
Ivan R. Corrêa
Domenico Bosco
Paul R. Johnson
Lorenzo Piemonti
Piero Marchetti
A. M.James Shapiro
Blake J. Cochran
Aylin C. Hanyaloglu
Asuka Inoue
Tricia Tan
Guy A. Rutter
Alejandra Tomas
Stephen R. Bloom
Other Contributor(s)
IRCCS San Raffaele Scientific Institute
University of Alberta
Università di Pisa
New England Biolabs
University of New South Wales (UNSW) Australia
University of Oxford
Faculty of Medicine, Ramathibodi Hospital, Mahidol University
Imperial College London
Università Vita-Salute San Raffaele
Tohoku University
Université de Genève
University of Alberta
Università di Pisa
New England Biolabs
University of New South Wales (UNSW) Australia
University of Oxford
Faculty of Medicine, Ramathibodi Hospital, Mahidol University
Imperial College London
Università Vita-Salute San Raffaele
Tohoku University
Université de Genève
Abstract
© 2018 The Author(s). Glucagon-like peptide-1 receptor (GLP-1R) activation promotes insulin secretion from pancreatic beta cells, causes weight loss, and is an important pharmacological target in type 2 diabetes (T2D). Like other G protein-coupled receptors, the GLP-1R undergoes agonist-mediated endocytosis, but the functional and therapeutic consequences of modulating GLP-1R endocytic trafficking have not been clearly defined. Here, we investigate a series of biased GLP-1R agonists with variable propensities for GLP-1R internalization and recycling. Compared to a panel of FDA-approved GLP-1 mimetics, compounds that retain GLP-1R at the plasma membrane produce greater long-term insulin release, which is dependent on a reduction in β-arrestin recruitment and faster agonist dissociation rates. Such molecules elicit glycemic benefits in mice without concomitant increases in signs of nausea, a common side effect of GLP-1 therapies. Our study identifies a set of agents with specific GLP-1R trafficking profiles and the potential for greater efficacy and tolerability as T2D treatments.