Imperial College London
Portrait Picture

ProfessorAylinHanyaloglu

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Professor in Molecular Medicine
 
 
 
//

Contact

 

+44 (0)20 7594 2128a.hanyaloglu Website

 
 
//

Assistant

 

Miss Kiran Dosanjh +44 (0)20 7594 2176

 
//

Location

 

2009Institute of Reproductive and Developmental BiologyHammersmith Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Jones:2018:10.1038/s41467-018-03941-2,
author = {Jones, B and Buenaventura, T and Kanda, N and Chabosseau, P and Owen, B and Scott, R and Goldin, R and Angkathunyakul, N and Correa, Jr IR and Bosco, D and Johnson, PR and Piemonti, L and Marchetti, P and Shapiro, AMJ and Cochran, B and Hanyaloglu, A and Inoue, A and Tan, T and Rutter, G and Tomas, Catala A and Bloom, S},
doi = {10.1038/s41467-018-03941-2},
journal = {Nature Communications},
title = {Targeting GLP-1 receptor trafficking to improve agonist efficacy},
url = {http://dx.doi.org/10.1038/s41467-018-03941-2},
volume = {9},
year = {2018}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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 novel 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.
AU  - Jones,B
AU  - Buenaventura,T
AU  - Kanda,N
AU  - Chabosseau,P
AU  - Owen,B
AU  - Scott,R
AU  - Goldin,R
AU  - Angkathunyakul,N
AU  - Correa,Jr IR
AU  - Bosco,D
AU  - Johnson,PR
AU  - Piemonti,L
AU  - Marchetti,P
AU  - Shapiro,AMJ
AU  - Cochran,B
AU  - Hanyaloglu,A
AU  - Inoue,A
AU  - Tan,T
AU  - Rutter,G
AU  - Tomas,Catala A
AU  - Bloom,S
DO  - 10.1038/s41467-018-03941-2
PY  - 2018///
SN  - 2041-1723
TI  - Targeting GLP-1 receptor trafficking to improve agonist efficacy
T2  - Nature Communications
UR  - http://dx.doi.org/10.1038/s41467-018-03941-2
UR  - https://www.nature.com/articles/s41467-018-03941-2
UR  - http://hdl.handle.net/10044/1/57825
VL  - 9
ER  -
Download