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

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.

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Consejeria de Salud PI-0727-2010 P10CTS6505

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Fundacion Publica Andaluza Progreso y Salud PI-0727-2010 P10CTS6505

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Junta de Andalucia PI-0727-2010 P10CTS6505

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Consejeria de Economia, Innovacion y Ciencia P10.CTS.6359

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Ministerio de Economía y Competitividad PI10/00871 PI13/00593 BFU2017-83588-P PI14/01015 RD12/0019/0028 RD16/0011/0034 PI16/00259

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Fondos Feder PI10/00871 PI13/00593 BFU2017-83588-P PI14/01015 RD12/0019/0028 RD16/0011/0034 PI16/00259

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Deutsche Forschungsgemeinschaft GRK-1789 SCHI-505/ 6-1

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Instituto de Salud Carlos III CP14/ 00105

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Fondos FEDER CP14/ 00105

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Juvenile Diabetes Research Foundation 17-2013-372 3-RSC-2016-162-I-X

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