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

Cobo-Vuilleumier, Nadia
Lorenzo, Petra I
Rodríguez, Noelia García
Herrera Gómez, Irene de Gracia
Fuente-Martin, Esther
López-Noriega, Livia
Mellado-Gil, José Manuel
Romero-Zerbo, Silvana-Yanina
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Published in Nature communications. 2018, vol. 9, no. 1, 1488
Abstract 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.
Keywords AnimalsApoptosis/drug effectsCell Communication/drug effectsCell Survival/drug effectsDiabetes MellitusExperimental/chemically induced/genetics/immunology/therapyDiabetes MellitusType 2/genetics/immunology/pathologyFemaleGene Expression RegulationHumansHypoglycemic Agents/pharmacologyImmunityInnateInsulin/metabolismInsulin-Secreting Cells/drug effects/immunology/pathologyIslets of Langerhans/drug effects/immunology/pathologyIslets of Langerhans TransplantationMacrophages/drug effects/immunology/pathologyMaleMiceMiceInbred C57BLPhenalenes/pharmacologyReceptorsCytoplasmic and Nuclear/agonists/genetics/immunologyStreptozocinT-LymphocytesRegulatory/drug effects/immunology/pathologyTransplantationHeterologous
PMID: 29662071
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Research group La transplantation d'îlots de Langerhans (623)
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COBO-VUILLEUMIER, Nadia et al. LRH-1 agonism favours an immune-islet dialogue which protects against diabetes mellitus. In: Nature Communications, 2018, vol. 9, n° 1, p. 1488. doi: 10.1038/s41467-018-03943-0 https://archive-ouverte.unige.ch/unige:119421

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Deposited on : 2019-06-17

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