RT info:eu-repo/semantics/article
T1 LRH-1 agonism favours an immune-islet dialogue which protects against diabetes mellitus
A1 Cobo Vuilleumier, Nadia .
A1 Lorenzo, Petra Isabel .
A1 García Rodríguez, Noelia .
A1 Gracia Herrera-Gómez, Irene de .
A1 Fuente Martín, Esther .
A1 López Noriega, Livia
A1 Mellado Gil, José Manuel .
A1 Romero Zerbo, Silvana-Yanina .
A1 Baquié, Mathurin .
A1 Lachaud, Christian Claude .
A1 Stifter, Katja .
A1 Perdomo Hernández, Germán M.
A1 Bugliani, Marco .
A1 Tata, Vincenzo de .
A1 Bosco, Domenico .
A1 Parnaud, Geraldine .
A1 Pozo, David .
A1 Hmadcha, Abdelkrim .
A1 Florido, Javier P. .
A1 Toscano, Miguel G. .
A1 Haan, Peter de .
A1 Schoonjans, Kristina .
A1 Sánchez Palazón, Luis .
A1 Marchetti, Piero .
A1 Schirmbeck, Reinhold .
A1 Martín Montalvo, Alejandro .
A1 Meda, Paolo .
A1 Soria, Bernat .
A1 Bermúdez Silva, Francisco Javier .
A1 St-Onge16, Luc .
A1 Gauthier, Benoit R. .
K1 Endocrinología
K1 Endocrinology
AB 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.
PB Springer Nature
SN 2041-1723
YR 2018
FD 2018-04
LK http://hdl.handle.net/10259/4993
UL http://hdl.handle.net/10259/4993
LA eng
NO the Juvenile Diabetes Research Foundation (17-2013-372 to B.R.G.), theConsejeria 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, Innovaciony Ciencia (P10.CTS.6359 to B.R.G.), the Ministerio de Economia y Competidividad cofundedby 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 graciouslysupported 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 fellowshipfrom Amarna Therapeutics. In some instances, human islets were procured through theEuropean Consortium for Islet Transplantation funded by Juvenile Diabetes ResearchFoundation (3-RSC-2016-162-I-X).
DS Repositorio Institucional de la Universidad de Burgos
RD 27-abr-2024