Journal
JOURNAL OF ENDOCRINOLOGY
Volume 225, Issue 2, Pages 77-88Publisher
BIOSCIENTIFICA LTD
DOI: 10.1530/JOE-15-0010
Keywords
glucose metabolism; high-fat diet; skeletal muscle; myotubes
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Funding
- Thompson Fellowship, University of Sydney
- Cumberland Research Grant (University of Sydney)
- Novo Nordisk Foundation
- Albert Renold Travel Fellowship (European Foundation for the Study of Diabetes)
- NNF Center for Basic Metabolic Research [Barres Group] Funding Source: researchfish
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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.
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