LRH-1 agonism favours an immune-islet dialogue which protects against diabetes mellitus

Cobo Vuilleumier, Nadia; Lorenzo, Petra I.; García Rodríguez, Noelia; Herrera Gómez, Irene G.; Fuente Martín, Esther; López Noriega, Livia; Mellado Gil, José Manuel; Romero Zerbo, Silvana Y.; Lachaud, Christian; Hmadcha, Abdelkrim; Sánchez Palazón, Luis; Martín Montalvo, Alejandro; Soria Escoms, Bernat; Gauthier, Benoit R.

LRH-1 agonism favours an immune-islet dialogue which protects against diabetes mellitus

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 dam...

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Detalhes bibliográficos
Autores:	Cobo Vuilleumier, Nadia, Lorenzo, Petra I., García Rodríguez, Noelia, Herrera Gómez, Irene G., Fuente Martín, Esther, López Noriega, Livia, Mellado Gil, José Manuel, Romero Zerbo, Silvana Y., Lachaud, Christian, Hmadcha, Abdelkrim, Sánchez Palazón, Luis, Martín Montalvo, Alejandro, Soria Escoms, Bernat, Gauthier, Benoit R.
Formato:	artículo
Estado:	Versión publicada
Fecha de publicación:	2018
País:	España
Recursos:	Universidad de Sevilla (US)
Repositorio:	idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:	oai:idus.us.es:11441/75219
Acesso em linha:	https://hdl.handle.net/11441/75219 https://doi.org/10.1038/s41467-018-03943-0
Access Level:	acceso abierto
Palavra-chave:	Islets of Langerhans Type 1 diabetes Type 2 diabetes

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spelling	LRH-1 agonism favours an immune-islet dialogue which protects against diabetes mellitusCobo Vuilleumier, NadiaLorenzo, Petra I.García Rodríguez, NoeliaHerrera Gómez, Irene G.Fuente Martín, EstherLópez Noriega, LiviaMellado Gil, José ManuelRomero Zerbo, Silvana Y.Lachaud, ChristianHmadcha, AbdelkrimSánchez Palazón, LuisMartín Montalvo, AlejandroSoria Escoms, BernatGauthier, Benoit R.Islets of LangerhansType 1 diabetesType 2 diabetesType 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.Consejeria de Salud PI-0727-2010 P10CTS6505Fundacion Publica Andaluza Progreso y Salud PI-0727-2010 P10CTS6505Junta de Andalucia PI-0727-2010 P10CTS6505Consejeria de Economia, Innovacion y Ciencia P10.CTS.6359Ministerio de Economía y Competitividad PI10/00871 PI13/00593 BFU2017-83588-P PI14/01015 RD12/0019/0028 RD16/0011/0034 PI16/00259Fondos Feder PI10/00871 PI13/00593 BFU2017-83588-P PI14/01015 RD12/0019/0028 RD16/0011/0034 PI16/00259Deutsche Forschungsgemeinschaft GRK-1789 SCHI-505/ 6-1Instituto de Salud Carlos III CP14/ 00105Fondos FEDER CP14/ 00105Juvenile Diabetes Research Foundation 17-2013-372 3-RSC-2016-162-I-XNature Publishing GroupCentro Andaluz de Investigaciones en Biología Molecular y Medicina Regenerativa (CABIMER)2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttps://hdl.handle.net/11441/75219https://doi.org/10.1038/s41467-018-03943-0reponame:idUS. Depósito de Investigación de la Universidad de Sevillainstname:Universidad de Sevilla (US)InglésNature Communications, 9 (1), 1488-1-1488-15.PI-0727-2010P10CTS6505P10.CTS.6359PI10/00871PI13/00593BFU2017-83588-PPI14/01015RD12/0019/0028RD16/0011/0034PI16/00259GRK-1789SCHI-505/ 6-1CP14/ 0010517-2013-3723-RSC-2016-162-I-Xhttp://doi.org/10.1038/s41467-018-03943-0info:eu-repo/semantics/openAccessoai:idus.us.es:11441/752192026-06-17T12:51:07Z
dc.title.none.fl_str_mv	LRH-1 agonism favours an immune-islet dialogue which protects against diabetes mellitus
title	LRH-1 agonism favours an immune-islet dialogue which protects against diabetes mellitus
spellingShingle	LRH-1 agonism favours an immune-islet dialogue which protects against diabetes mellitus Cobo Vuilleumier, Nadia Islets of Langerhans Type 1 diabetes Type 2 diabetes
title_short	LRH-1 agonism favours an immune-islet dialogue which protects against diabetes mellitus
title_full	LRH-1 agonism favours an immune-islet dialogue which protects against diabetes mellitus
title_fullStr	LRH-1 agonism favours an immune-islet dialogue which protects against diabetes mellitus
title_full_unstemmed	LRH-1 agonism favours an immune-islet dialogue which protects against diabetes mellitus
title_sort	LRH-1 agonism favours an immune-islet dialogue which protects against diabetes mellitus
dc.creator.none.fl_str_mv	Cobo Vuilleumier, Nadia Lorenzo, Petra I. García Rodríguez, Noelia Herrera Gómez, Irene G. Fuente Martín, Esther López Noriega, Livia Mellado Gil, José Manuel Romero Zerbo, Silvana Y. Lachaud, Christian Hmadcha, Abdelkrim Sánchez Palazón, Luis Martín Montalvo, Alejandro Soria Escoms, Bernat Gauthier, Benoit R.
author	Cobo Vuilleumier, Nadia
author_facet	Cobo Vuilleumier, Nadia Lorenzo, Petra I. García Rodríguez, Noelia Herrera Gómez, Irene G. Fuente Martín, Esther López Noriega, Livia Mellado Gil, José Manuel Romero Zerbo, Silvana Y. Lachaud, Christian Hmadcha, Abdelkrim Sánchez Palazón, Luis Martín Montalvo, Alejandro Soria Escoms, Bernat Gauthier, Benoit R.
author_role	author
author2	Lorenzo, Petra I. García Rodríguez, Noelia Herrera Gómez, Irene G. Fuente Martín, Esther López Noriega, Livia Mellado Gil, José Manuel Romero Zerbo, Silvana Y. Lachaud, Christian Hmadcha, Abdelkrim Sánchez Palazón, Luis Martín Montalvo, Alejandro Soria Escoms, Bernat Gauthier, Benoit R.
author2_role	author author author author author author author author author author author author author
dc.contributor.none.fl_str_mv	Centro Andaluz de Investigaciones en Biología Molecular y Medicina Regenerativa (CABIMER)
dc.subject.none.fl_str_mv	Islets of Langerhans Type 1 diabetes Type 2 diabetes
topic	Islets of Langerhans Type 1 diabetes Type 2 diabetes
description	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.
publishDate	2018
dc.date.none.fl_str_mv	2018
dc.type.none.fl_str_mv	info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion
format	article
status_str	publishedVersion
dc.identifier.none.fl_str_mv	https://hdl.handle.net/11441/75219 https://doi.org/10.1038/s41467-018-03943-0
url	https://hdl.handle.net/11441/75219 https://doi.org/10.1038/s41467-018-03943-0
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.relation.none.fl_str_mv	Nature Communications, 9 (1), 1488-1-1488-15. PI-0727-2010 P10CTS6505 P10.CTS.6359 PI10/00871 PI13/00593 BFU2017-83588-P PI14/01015 RD12/0019/0028 RD16/0011/0034 PI16/00259 GRK-1789 SCHI-505/ 6-1 CP14/ 00105 17-2013-372 3-RSC-2016-162-I-X http://doi.org/10.1038/s41467-018-03943-0
dc.rights.none.fl_str_mv	info:eu-repo/semantics/openAccess
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	application/pdf application/pdf
dc.publisher.none.fl_str_mv	Nature Publishing Group
publisher.none.fl_str_mv	Nature Publishing Group
dc.source.none.fl_str_mv	reponame:idUS. Depósito de Investigación de la Universidad de Sevilla instname:Universidad de Sevilla (US)
instname_str	Universidad de Sevilla (US)
reponame_str	idUS. Depósito de Investigación de la Universidad de Sevilla
collection	idUS. Depósito de Investigación de la Universidad de Sevilla
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score	15,301603

LRH-1 agonism favours an immune-islet dialogue which protects against diabetes mellitus

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