2026-10-15T05:59:45Zhttps://riubu.ubu.es/oai/requestoai:riubu.ubu.es:10259/49932021-11-10T09:38:26Zcom_10259_4725com_10259_5086com_10259_2604col_10259_4726
Cobo Vuilleumier, Nadia .
Lorenzo, Petra Isabel .
García Rodríguez, Noelia .
Gracia Herrera-Gómez, Irene de .
Fuente Martín, Esther .
López Noriega, Livia
Mellado Gil, José Manuel .
Romero Zerbo, Silvana-Yanina .
Baquié, Mathurin .
Lachaud, Christian Claude .
Stifter, Katja .
Perdomo Hernández, Germán M.
Bugliani, Marco .
Tata, Vincenzo de .
Bosco, Domenico .
Parnaud, Geraldine .
Pozo, David .
Hmadcha, Abdelkrim .
Florido, Javier P. .
Toscano, Miguel G. .
Haan, Peter de .
Schoonjans, Kristina .
Sánchez Palazón, Luis .
Marchetti, Piero .
Schirmbeck, Reinhold .
Martín Montalvo, Alejandro .
Meda, Paolo .
Soria, Bernat .
Bermúdez Silva, Francisco Javier .
St-Onge16, Luc .
Gauthier, Benoit R. .
2018-10-31T12:38:16Z
2018-10-31T12:38:16Z
2018-04
2041-1723
http://hdl.handle.net/10259/4993
10.1038/s41467-018-03943-0
Type 1 diabetes mellitus (T1DM) is due to the selective destruction of islet beta cells by immune cells. Current therapies focused on repressing the immune attack or stimulating beta cell regeneration still have limited clinical efficacy. Therefore, it is timely to identify innovative targets to dampen the immune process, while promoting beta cell survival and function. Liver receptor homologue-1 (LRH-1) is a nuclear receptor that represses inflammation in digestive organs, and protects pancreatic islets against apoptosis. Here, we show that BL001, a small LRH-1 agonist, impedes hyperglycemia progression and the immune-dependent inflammation of pancreas in murine models of T1DM, and beta cell apoptosis in islets of type 2 diabetic patients, while increasing beta cell mass and insulin secretion. Thus, we suggest that LRH-1 agonism favors a dialogue between immune and islet cells, which could be druggable to protect against diabetes mellitus.
the Juvenile Diabetes Research Foundation (17-2013-372 to B.R.G.), the
Consejeria de Salud, Fundacion Publica Andaluza Progreso y Salud, Junta de Andalucia
(PI-0727-2010 to B.R.G. and P10CTS6505 to B.S.), Consejeria de Economia, Innovacion
y Ciencia (P10.CTS.6359 to B.R.G.), the Ministerio de Economia y Competidividad cofunded
by Fondos FEDER (PI10/00871, PI13/00593, and BFU2017-83588-P to B.R.G.;
PI14/01015, RD12/0019/0028, and RD16/0011/0034 to B.S.; PI16/00259 to A.
H.) and Deutsche Forschungsgemeinschaft (GRK-1789 ´CEMMA´ and DFG SCHI-505/
6-1 to R.S.). Special thanks to the families of the DiabetesCero Foundation that graciously
supported this work (to B.R.G.). A.M.M. is a recipient of a Miguel Servet grant (CP14/
00105) from the Instituto de Salud Carlos III co-funded by Fondos FEDER whereas E.F.
M. is a recipient of a Juan de la Cierva Fellowship. I.G.H.G. is supported by a fellowship
from Amarna Therapeutics. In some instances, human islets were procured through the
European Consortium for Islet Transplantation funded by Juvenile Diabetes Research
Foundation (3-RSC-2016-162-I-X).
application/pdf
eng
Springer Nature
Nature Communications. 2018, V. 9, n.1, 1488
http://dx.doi.org/10.1038/s41467-018-03943-0
info:eu-repo/grantAgreement/JuvenileDiabetesResearchFoundation/17-2013-372
info:eu-repo/grantAgreement/JA/PI-0727-2010
info:eu-repo/grantAgreement/JA/P10CTS6505
info:eu-repo/grantAgreement/MINECO/PI10/00871
info:eu-repo/grantAgreement/MINECO/PI13/00593
info:eu-repo/grantAgreement/MINECO/BFU2017-83588-P
info:eu-repo/grantAgreement/MINECO/PI14/01015
info:eu-repo/grantAgreement/MINECO/RD12/0019/0028
info:eu-repo/grantAgreement/MINECO/RD16/0011/0034
info:eu-repo/grantAgreement/MINECO/PI16/00259
info:eu-repo/grantAgreement/DeutscheForschungsgemeinschaft/GRK-1789
info:eu-repo/grantAgreement/DeutscheForschungsgemeinschaft/DFG SCHI-505/
6-1
Attribution 4.0 International
http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
Endocrinología
Endocrinology
LRH-1 agonism favours an immune-islet dialogue which protects against diabetes mellitus
info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion