TY - JOUR T1 - LRH-1 agonism favours an immune-islet dialogue which protects against diabetes mellitus. JF - Nat Commun Y1 - 2018 A1 - Cobo-Vuilleumier, Nadia A1 - Lorenzo, Petra I A1 - Rodríguez, Noelia García A1 - Herrera Gómez, Irene de Gracia A1 - Fuente-Martin, 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, German A1 - Bugliani, Marco A1 - De Tata, Vincenzo A1 - Bosco, Domenico A1 - Parnaud, Geraldine A1 - Pozo, David A1 - Hmadcha, Abdelkrim A1 - Florido, Javier P A1 - Toscano, Miguel G A1 - de Haan, Peter 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-Onge, Luc A1 - Gauthier, Benoit R KW - Animals KW - Apoptosis KW - Cell Communication KW - Cell Survival KW - Diabetes Mellitus, Experimental KW - Diabetes Mellitus, Type 2 KW - Female KW - Gene Expression Regulation KW - Humans KW - Hypoglycemic Agents KW - Immunity, Innate KW - insulin KW - Insulin-Secreting Cells KW - Islets of Langerhans KW - Islets of Langerhans Transplantation KW - Macrophages KW - Male KW - Mice KW - Mice, Inbred C57BL KW - Phenalenes KW - Receptors, Cytoplasmic and Nuclear KW - Streptozocin KW - T-Lymphocytes, Regulatory KW - Transplantation, Heterologous 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.

VL - 9 IS - 1 U1 - https://www.ncbi.nlm.nih.gov/pubmed/29662071?dopt=Abstract ER -