Imperial College London
Alternate

Professor Sir Steve Bloom FMedSci, FRS

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Departmental Academic REF2014 Lead
 
 
 
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Contact

 

+44 (0)20 7594 9048s.bloom Website

 
 
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Assistant

 

Ms Keda Price-Cousins +44 (0)20 7594 9048

 
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Location

 

6N3Commonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Jones:2020:10.1101/2020.04.26.062372,
author = {Jones, B and McGlone, ER and Fang, Z and Pickford, P and Corrêa, IR and Oishi, A and Jockers, R and Inoue, A and Kumar, S and Görlitz, F and Dunsby, C and French, PMW and Rutter, GA and Tan, T and Tomas, A and Bloom, SR},
doi = {10.1101/2020.04.26.062372},
title = {Signal bias at glucagon family receptors: rationale and downstream impacts},
url = {http://dx.doi.org/10.1101/2020.04.26.062372},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - <jats:title>Abstract</jats:title><jats:p>Receptors for the peptide hormones glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and glucagon (GCG) are important regulators of insulin secretion and energy metabolism. Recently described GLP-1 receptor agonists showing signal bias in favour of cyclic AMP over β-arrestin-2 recruitment have delivered promising results in preclinical studies. Here we first sought to establish the role of β-arrestins in the control of intracellular signalling and trafficking responses at the closely related GLP-1, GIP and GCG receptors, through studies performed in cells depleted of both β-arrestin isoforms. We also generated analogues of GLP-1, GCG and GIP which in some cases showed selective reduction in β-arrestin-2 recruitment <jats:italic>versus</jats:italic> cAMP signalling compared to the parent peptide. Despite reduced acute signalling potency and/or efficacy, some biased GLP-1 and GIP analogues increased maximal sustained insulin secretion from INS-1 832/3 clonal beta cells, although only at high agonist concentrations. Biased GCG analogues did not affect maximal insulin release, or glucose output in hepatocytes.</jats:p>
AU  - Jones,B
AU  - McGlone,ER
AU  - Fang,Z
AU  - Pickford,P
AU  - Corrêa,IR
AU  - Oishi,A
AU  - Jockers,R
AU  - Inoue,A
AU  - Kumar,S
AU  - Görlitz,F
AU  - Dunsby,C
AU  - French,PMW
AU  - Rutter,GA
AU  - Tan,T
AU  - Tomas,A
AU  - Bloom,SR
DO  - 10.1101/2020.04.26.062372
PY  - 2020///
TI  - Signal bias at glucagon family receptors: rationale and downstream impacts
UR  - http://dx.doi.org/10.1101/2020.04.26.062372
ER  -
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