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

Author

Listed:
  • Nadia Cobo-Vuilleumier

    (Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC)

  • Petra I. Lorenzo

    (Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC)

  • Noelia García Rodríguez

    (Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC)

  • Irene de Gracia Herrera Gómez

    (Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC)

  • Esther Fuente-Martin

    (Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC)

  • Livia López-Noriega

    (Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC)

  • José Manuel Mellado-Gil

    (Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC)

  • Silvana-Yanina Romero-Zerbo

    (Universidad de Málaga
    Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM))

  • Mathurin Baquié

    (Neurix SA)

  • Christian Claude Lachaud

    (Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC)

  • Katja Stifter

    (Ulm University Hospital)

  • German Perdomo

    (Universidad de Burgos)

  • Marco Bugliani

    (University of Pisa—AOUP University Hospital)

  • Vincenzo De Tata

    (University of Pisa)

  • Domenico Bosco

    (University Hospital)

  • Geraldine Parnaud

    (University Hospital)

  • David Pozo

    (CABIMER-Andalusian Center for Molecular Biology and Regenerative Medicine)

  • Abdelkrim Hmadcha

    (Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC
    Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM))

  • Javier P. Florido

    (Consejería de Salud)

  • Miguel G. Toscano

    (Amarna Therapeutics)

  • Peter de Haan

    (Amarna Therapeutics)

  • Kristina Schoonjans

    (EPFL)

  • Luis Sánchez Palazón

    (CABIMER-Andalusian Center for Molecular Biology and Regenerative Medicine)

  • Piero Marchetti

    (University of Pisa—AOUP University Hospital)

  • Reinhold Schirmbeck

    (Ulm University Hospital)

  • Alejandro Martín-Montalvo

    (Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC)

  • Paolo Meda

    (University of Geneva)

  • Bernat Soria

    (Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC
    Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM))

  • Francisco-Javier Bermúdez-Silva

    (Universidad de Málaga
    Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM))

  • Luc St-Onge
  • Benoit R. Gauthier

    (Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC)

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.

Suggested Citation

  • Nadia Cobo-Vuilleumier & Petra I. Lorenzo & Noelia García Rodríguez & Irene de Gracia Herrera Gómez & Esther Fuente-Martin & Livia López-Noriega & José Manuel Mellado-Gil & Silvana-Yanina Romero-Zerbo, 2018. "LRH-1 agonism favours an immune-islet dialogue which protects against diabetes mellitus," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03943-0
    DOI: 10.1038/s41467-018-03943-0
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    Cited by:

    1. Francesca D’Addio & Anna Maestroni & Emma Assi & Moufida Ben Nasr & Giovanni Amabile & Vera Usuelli & Cristian Loretelli & Federico Bertuzzi & Barbara Antonioli & Francesco Cardarelli & Basset El Essa, 2022. "The IGFBP3/TMEM219 pathway regulates beta cell homeostasis," Nature Communications, Nature, vol. 13(1), pages 1-14, December.

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