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dc.contributor.authorCobo Vuilleumier, Nadia .
dc.contributor.authorLorenzo, Petra Isabel .
dc.contributor.authorGarcía Rodríguez, Noelia .
dc.contributor.authorGracia Herrera-Gómez, Irene de .
dc.contributor.authorFuente Martín, Esther .
dc.contributor.authorLópez Noriega, Livia
dc.contributor.authorMellado Gil, José Manuel .
dc.contributor.authorRomero Zerbo, Silvana-Yanina .
dc.contributor.authorBaquié, Mathurin .
dc.contributor.authorLachaud, Christian Claude .
dc.contributor.authorStifter, Katja .
dc.contributor.authorPerdomo Hernández, Germán M. 
dc.contributor.authorBugliani, Marco .
dc.contributor.authorTata, Vincenzo de .
dc.contributor.authorBosco, Domenico .
dc.contributor.authorParnaud, Geraldine .
dc.contributor.authorPozo, David .
dc.contributor.authorHmadcha, Abdelkrim .
dc.contributor.authorFlorido, Javier P. .
dc.contributor.authorToscano, Miguel G. .
dc.contributor.authorHaan, Peter de .
dc.contributor.authorSchoonjans, Kristina .
dc.contributor.authorSánchez Palazón, Luis .
dc.contributor.authorMarchetti, Piero .
dc.contributor.authorSchirmbeck, Reinhold .
dc.contributor.authorMartín Montalvo, Alejandro .
dc.contributor.authorMeda, Paolo .
dc.contributor.authorSoria, Bernat .
dc.contributor.authorBermúdez Silva, Francisco Javier .
dc.contributor.authorSt-Onge16, Luc .
dc.contributor.authorGauthier, Benoit R. .
dc.date.accessioned2018-10-31T12:38:16Z
dc.date.available2018-10-31T12:38:16Z
dc.date.issued2018-04
dc.identifier.issn2041-1723
dc.identifier.urihttp://hdl.handle.net/10259/4993
dc.description.abstractType 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.en
dc.description.sponsorshipthe 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).en
dc.format.mimetypeapplication/pdf
dc.language.isoenges
dc.publisherSpringer Natureen
dc.relation.ispartofNature Communications. 2018, V. 9, n.1, 1488en
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subject.otherEndocrinologíaes
dc.subject.otherEndocrinologyen
dc.titleLRH-1 agonism favours an immune-islet dialogue which protects against diabetes mellitusen
dc.typeinfo:eu-repo/semantics/article
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.relation.publisherversionhttp://dx.doi.org/10.1038/s41467-018-03943-0
dc.identifier.doi10.1038/s41467-018-03943-0
dc.relation.projectIDinfo:eu-repo/grantAgreement/JuvenileDiabetesResearchFoundation/17-2013-372
dc.relation.projectIDinfo:eu-repo/grantAgreement/JA/PI-0727-2010
dc.relation.projectIDinfo:eu-repo/grantAgreement/JA/P10CTS6505
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO/PI10/00871
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO/PI13/00593
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO/BFU2017-83588-P
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO/PI14/01015
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO/RD12/0019/0028
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO/RD16/0011/0034
dc.relation.projectIDinfo:eu-repo/grantAgreement/MINECO/PI16/00259
dc.relation.projectIDinfo:eu-repo/grantAgreement/DeutscheForschungsgemeinschaft/GRK-1789
dc.relation.projectIDinfo:eu-repo/grantAgreement/DeutscheForschungsgemeinschaft/DFG SCHI-505/ 6-1
dc.type.hasVersioninfo:eu-repo/semantics/publishedVersionen


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