Elastin-derived peptides are new regulators of insulin resistance development in mice

Sébastien Blaise, Béatrice Romier, Charlotte Kawecki, Maxime Ghirardi, Fanja Rabenoelina, Stéphanie Baud, Laurent Duca, Pascal Maurice, Andrea Heinz, Christian E H Schmelzer, Michel Tarpin, Laurent Martiny, Christian Garbar, Manuel Dauchez, Laurent Debelle, Vincent Durlach

    56 Citationer (Scopus)

    Abstract

    Although it has long been established that the extracellular matrix acts as a mechanical support, its degradation products, which mainly accumulate during aging, have also been demonstrated to play an important role in cell physiology and the development of cardiovascular and metabolic diseases. In the current study, we show that elastin-derived peptides (EDPs) may be involved in the development of insulin resistance (IRES) in mice. In chow-fed mice, acute or chronic intravenous injections of EDPs induced hyperglycemic effects associated with glucose uptake reduction and IRES in skeletal muscle, liver, and adipose tissue. Based on in vivo, in vitro, and in silico approaches, we propose that this IRES is due to interaction between the insulin receptor (IR) and the neuraminidase-1 subunit of the elastin receptor complex triggered by EDPs. This interplay was correlated with decreased sialic acid levels on the b-chain of the IR and reduction of IR signaling. In conclusion, this is the first study to demonstrate that EDPs, which mainly accumulate with aging, may be involved in the insidious development of IRES.

    OriginalsprogEngelsk
    TidsskriftDiabetes
    Vol/bind62
    Udgave nummer11
    Sider (fra-til)3807-16
    Antal sider10
    ISSN0012-1797
    DOI
    StatusUdgivet - nov. 2013

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