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    Blockade of receptor activator of nuclear factor-κB (RANKL) signaling improves hepatic insulin resistance and prevents development of diabetes mellitus

    The authors examined if receptor activator of NF-κB ligand (RANKL), a prototypic activator of NF-κB, contributes to the development of type 2 diabetes mellitus (T2DM) using both an epidemiological and experimental approach. In the prospective population-based study they found that a high serum concentration of soluble RANKL was a significant (P < 0.001) and independent predictor of T2DM manifestation. Furthermore, systemic or hepatic blockade of RANKL signaling in mouse models of T2DM caused a marked improvement of plasma glucose concentrations and glucose tolerance.

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    Stefan Kiechl, Jürgen Wittmann, Andrea Giaccari, Michael Knoflach, Peter Willeit, Aline Bozec, et al