Chronic erythropoietin treatment improves diet-induced glucose intolerance in rats

TY - JOUR

T1 - Chronic erythropoietin treatment improves diet-induced glucose intolerance in rats

AU - Caillaud, Corinne

AU - Mechta, Mie

AU - Ainge, Heidi

AU - Madsen, Andreas Nygaard

AU - Ruell, Patricia

AU - Mas, Emilie

AU - Bisbal, Catherine

AU - Mercier, Jacques

AU - Twigg, Stephen

AU - Mori, Trevor A

AU - Simar, David

AU - Barrès, Romain

N1 - © 2015 The authors.

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

U2 - 10.1530/JOE-15-0010

DO - 10.1530/JOE-15-0010

M3 - Journal article

C2 - 25767056

SN - 0022-0795

VL - 225

SP - 77

EP - 88

JO - Journal of Endocrinology

JF - Journal of Endocrinology

IS - 2

ER -