Imperial College London
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Dr Alejandra Tomas

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 3364a.tomas-catala Website CV

 
 
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Location

 

329ICTEM buildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Xu:2023:10.1016/j.celrep.2023.112529,
author = {Xu, W and Qadir, MMF and Nasteska, D and Mota, de Sa P and Gorvin, CM and Blandino-Rosano, M and Evans, CR and Ho, T and Potapenko, E and Veluthakal, R and Ashford, FB and Bitsi, S and Fan, J and Bhondeley, M and Song, K and Sure, VN and Sakamuri, SSVP and Schiffer, L and Beatty, W and Wyatt, R and Frigo, DE and Liu, X and Katakam, PV and Arlt, W and Buck, J and Levin, LR and Hu, T and Kolls, J and Burant, CF and Tomas, A and Merrins, MJ and Thurmond, DC and Bernal-Mizrachi, E and Hodson, DJ and Mauvais-Jarvis, F},
doi = {10.1016/j.celrep.2023.112529},
journal = {Cell Reports},
pages = {1--29},
title = {Architecture of androgen receptor pathways amplifying glucagon-like peptide-1 insulinotropic action in male pancreatic β cells},
url = {http://dx.doi.org/10.1016/j.celrep.2023.112529},
volume = {42},
year = {2023}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Male mice lacking the androgen receptor (AR) in pancreatic β cells exhibit blunted glucose-stimulated insulin secretion (GSIS), leading to hyperglycemia. Testosterone activates an extranuclear AR in β cells to amplify glucagon-like peptide-1 (GLP-1) insulinotropic action. Here, we examined the architecture of AR targets that regulate GLP-1 insulinotropic action in male β cells. Testosterone cooperates with GLP-1 to enhance cAMP production at the plasma membrane and endosomes via: (1) increased mitochondrial production of CO2, activating the HCO3--sensitive soluble adenylate cyclase; and (2) increased Gαs recruitment to GLP-1 receptor and AR complexes, activating transmembrane adenylate cyclase. Additionally, testosterone enhances GSIS in human islets via a focal adhesion kinase/SRC/phosphatidylinositol 3-kinase/mammalian target of rapamycin complex 2 actin remodeling cascade. We describe the testosterone-stimulated AR interactome, transcriptome, proteome, and metabolome that contribute to these effects. This study identifies AR genomic and non-genomic actions that enhance GLP-1-stimulated insulin exocytosis in male β cells.
AU  - Xu,W
AU  - Qadir,MMF
AU  - Nasteska,D
AU  - Mota,de Sa P
AU  - Gorvin,CM
AU  - Blandino-Rosano,M
AU  - Evans,CR
AU  - Ho,T
AU  - Potapenko,E
AU  - Veluthakal,R
AU  - Ashford,FB
AU  - Bitsi,S
AU  - Fan,J
AU  - Bhondeley,M
AU  - Song,K
AU  - Sure,VN
AU  - Sakamuri,SSVP
AU  - Schiffer,L
AU  - Beatty,W
AU  - Wyatt,R
AU  - Frigo,DE
AU  - Liu,X
AU  - Katakam,PV
AU  - Arlt,W
AU  - Buck,J
AU  - Levin,LR
AU  - Hu,T
AU  - Kolls,J
AU  - Burant,CF
AU  - Tomas,A
AU  - Merrins,MJ
AU  - Thurmond,DC
AU  - Bernal-Mizrachi,E
AU  - Hodson,DJ
AU  - Mauvais-Jarvis,F
DO  - 10.1016/j.celrep.2023.112529
EP  - 29
PY  - 2023///
SN  - 2211-1247
SP  - 1
TI  - Architecture of androgen receptor pathways amplifying glucagon-like peptide-1 insulinotropic action in male pancreatic β cells
T2  - Cell Reports
UR  - http://dx.doi.org/10.1016/j.celrep.2023.112529
UR  - https://www.ncbi.nlm.nih.gov/pubmed/37200193
UR  - https://www.sciencedirect.com/science/article/pii/S2211124723005405
UR  - http://hdl.handle.net/10044/1/106131
VL  - 42
ER  -
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