Imperial College London


Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Professor of Practice (Metabolic Medicine & Endocrinology)



+44 (0)20 3313 8038t.tan




6N6ECommonwealth BuildingHammersmith Campus






BibTex format

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 = {},
volume = {9},
year = {2018}

RIS format (EndNote, RefMan)

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 -
UR -
VL - 9
ER -