Imperial College London
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DrBenJones

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Clinical Senior Lecturer in Metabolic Medicine
 
 
 
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Contact

 

ben.jones

 
 
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Location

 

Hammersmith HospitalHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Arcones:2021:10.1186/s12915-021-00966-w,
author = {Arcones, AC and Vila-Bedmar, R and Mirasierra, M and Cruces-Sande, M and Vallejo, M and Jones, B and Tomas, A and Mayor, F and Murga, C},
doi = {10.1186/s12915-021-00966-w},
journal = {BMC Biology},
title = {GRK2 regulates GLP-1R-mediated early phase insulin secretion in vivo},
url = {http://dx.doi.org/10.1186/s12915-021-00966-w},
volume = {19},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUND: Insulin secretion from the pancreatic β-cell is finely modulated by different signals to allow an adequate control of glucose homeostasis. Incretin hormones such as glucagon-like peptide-1 (GLP-1) act as key physiological potentiators of insulin release through binding to the G protein-coupled receptor GLP-1R. Another key regulator of insulin signaling is the Ser/Thr kinase G protein-coupled receptor kinase 2 (GRK2). However, whether GRK2 affects insulin secretion or if GRK2 can control incretin actions in vivo remains to be analyzed. RESULTS: Using GRK2 hemizygous mice, isolated pancreatic islets, and model β-cell lines, we have uncovered a relevant physiological role for GRK2 as a regulator of incretin-mediated insulin secretion in vivo. Feeding, oral glucose gavage, or administration of GLP-1R agonists in animals with reduced GRK2 levels (GRK2+/- mice) resulted in enhanced early phase insulin release without affecting late phase secretion. In contrast, intraperitoneal glucose-induced insulin release was not affected. This effect was recapitulated in isolated islets and correlated with the increased size or priming efficacy of the readily releasable pool (RRP) of insulin granules that was observed in GRK2+/- mice. Using nanoBRET in β-cell lines, we found that stimulation of GLP-1R promoted GRK2 association to this receptor and that GRK2 protein and kinase activity were required for subsequent β-arrestin recruitment. CONCLUSIONS: Overall, our data suggest that GRK2 is an important negative modulator of GLP-1R-mediated insulin secretion and that GRK2-interfering strategies may favor β-cell insulin secretion specifically during the early phase, an effect that may carry interesting therapeutic applications.
AU  - Arcones,AC
AU  - Vila-Bedmar,R
AU  - Mirasierra,M
AU  - Cruces-Sande,M
AU  - Vallejo,M
AU  - Jones,B
AU  - Tomas,A
AU  - Mayor,F
AU  - Murga,C
DO  - 10.1186/s12915-021-00966-w
PY  - 2021///
SN  - 1741-7007
TI  - GRK2 regulates GLP-1R-mediated early phase insulin secretion in vivo
T2  - BMC Biology
UR  - http://dx.doi.org/10.1186/s12915-021-00966-w
UR  - https://www.ncbi.nlm.nih.gov/pubmed/33658023
UR  - http://hdl.handle.net/10044/1/87209
VL  - 19
ER  -
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