Chronic erythropoietin treatment improves diet-induced glucose intolerance in rats

Corinne Caillaud, Mie Mechta, Heidi Ainge, Andreas Nygaard Madsen, Patricia Ruell, Emilie Mas, Catherine Bisbal, Jacques Mercier, Stephen Twigg, Trevor A Mori, David Simar, Romain Barrès

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    Abstract

    Erythropoietin (EPO) ameliorates glucose metabolism through mechanisms not fully understood. In this study, we investigated the effect of EPO on glucose metabolism and insulin signaling in skeletal muscle. A 2-week EPO treatment of rats fed with a high-fat diet (HFD) improved fasting glucose levels and glucose tolerance, without altering total body weight or retroperitoneal fat mass. Concomitantly, EPO partially rescued insulin-stimulated AKT activation, reduced markers of oxidative stress, and restored heat-shock protein 72 expression in soleus muscles from HFD-fed rats. Incubation of skeletal muscle cell cultures with EPO failed to induce AKT phosphorylation and had no effect on glucose uptake or glycogen synthesis. We found that the EPO receptor gene was expressed in myotubes, but was undetectable in soleus. Together, our results indicate that EPO treatment improves glucose tolerance but does not directly activate the phosphorylation of AKT in muscle cells. We propose that the reduced systemic inflammation or oxidative stress that we observed after treatment with EPO could contribute to the improvement of whole-body glucose metabolism.

    Original languageEnglish
    JournalJournal of Endocrinology
    Volume225
    Issue number2
    Pages (from-to)77-88
    Number of pages12
    ISSN0022-0795
    DOIs
    Publication statusPublished - 2015

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