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00925njm 22002777a 4500 dc Cobo-Vuilleumier, Nadia author Lorenzo, Petra I. author García Rodríguez, Noelia author Herrera Gómez, Irene de Gracia author Fuente-Martin, Esther author López-Noriega, Livia author Mellado-Gil, José Manuel author Romero-Zerbo, Silvana-Yanina author Baquié, Mathurin author Lachaud, Christian Claude author Stifter, Katja author German, Perdomo author Marco, Bugliani author De Tata, Vincenzo author Bosco, Domenico author Parnaud, Geraldine author Pozo, David author Hmadcha, Abdelkrim author Florido, Javier P. author Toscano, Miguel G. author de Haan, Peter author Schoonjans, Kristina author Sánchez Palazón, Luis author Marchetti, Piero author Schirmbeck, Reinhold author Martín-Montalvo, Alejandro author Meda, Paolo author Soria, Bernat author Bermúdez-Silva, Francisco-Javier author St-Onge, Luc author Gauthier, Benoit R. author 2018-04-16 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. 10.1038/s41467-018-03943-0 2041-1723 Nature Communications http://hdl.handle.net/10668/2858 http://hdl.handle.net/20.500.12105/17588 Islets of Langerhans Type 1 diabetes Type 2 diabetes Islotes Pancreáticos Diabetes Mellitus Tipo 1 Diabetes Mellitus Tipo 2 Diabetes Mellitus Diabetes LRH-1 agonism favours an immune-islet dialogue which protects against diabetes mellitus