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S100A9 extends lifespan in insulin deficiency

Author

Listed:
  • Giorgio Ramadori

    (University of Geneva
    University of Geneva)

  • Sanda Ljubicic

    (University of Geneva
    University of Geneva)

  • Serena Ricci

    (University of Geneva
    University of Geneva)

  • Despoina Mikropoulou

    (University of Geneva
    University of Geneva)

  • Xavier Brenachot

    (University of Geneva
    University of Geneva)

  • Christelle Veyrat-Durebex

    (University of Geneva
    University of Geneva)

  • Ebru Aras

    (University of Geneva
    University of Geneva)

  • Rafael M. Ioris

    (University of Geneva
    University of Geneva)

  • Jordi Altirriba

    (University of Geneva
    University of Geneva)

  • Elisabeth Malle

    (University of Geneva
    University of Geneva)

  • Dirk Foell

    (University of Munster)

  • Thomas Vogl

    (University of Munster
    University of Munster)

  • Roberto Coppari

    (University of Geneva
    University of Geneva
    University of California, Irvine)

Abstract

Tens of millions suffer from insulin deficiency (ID); a defect leading to severe metabolic imbalance and death. The only means for management of ID is insulin therapy; yet, this approach is sub-optimal and causes life-threatening hypoglycemia. Hence, ID represents a great medical and societal challenge. Here we report that S100A9, also known as Calgranulin B or Myeloid-Related Protein 14 (MRP14), is a leptin-induced circulating cue exerting beneficial anti-diabetic action. In murine models of ID, enhanced expression of S100A9 alone (i.e. without administered insulin and/or leptin) slightly improves hyperglycemia, and normalizes key metabolic defects (e.g. hyperketonemia, hypertriglyceridemia, and increased hepatic fatty acid oxidation; FAO), and extends lifespan by at least a factor of two. Mechanistically, we report that Toll-Like Receptor 4 (TLR4) is required, at least in part, for the metabolic-improving and pro-survival effects of S100A9. Thus, our data identify the S100A9/TLR4 axis as a putative target for ID care.

Suggested Citation

  • Giorgio Ramadori & Sanda Ljubicic & Serena Ricci & Despoina Mikropoulou & Xavier Brenachot & Christelle Veyrat-Durebex & Ebru Aras & Rafael M. Ioris & Jordi Altirriba & Elisabeth Malle & Dirk Foell & , 2019. "S100A9 extends lifespan in insulin deficiency," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-11498-x
    DOI: 10.1038/s41467-019-11498-x
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    Cited by:

    1. Gloria Ursino & Giorgio Ramadori & Anna Höfler & Soline Odouard & Pryscila D. S. Teixeira & Florian Visentin & Christelle Veyrat-Durebex & Giulia Lucibello & Raquel Firnkes & Serena Ricci & Claudia R., 2022. "Hepatic non-parenchymal S100A9-TLR4-mTORC1 axis normalizes diabetic ketogenesis," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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