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Int J Biol Sci. 2017 Oct 17;13(10):1329-1340. doi: 10.7150/ijbs.19752. eCollection 2017.

Erythropoietin Reduces Insulin Resistance via Regulation of Its Receptor-Mediated Signaling Pathways in db/db Mice Skeletal Muscle.

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Division of Nephrology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Division of Nephrology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China.
Hemodialysis Center, Baoshan Branch of Shanghai No.1 People's Hospital, Shanghai, China.


Erythropoietin (EPO) can reduce insulin resistance (IR) in adipocytes; however, it is unknown whether EPO can decrease IR in skeletal muscle. Here we investigated whether EPO could reduce IR in type 2 diabetic mouse skeletal muscle and its possible signaling mechanisms of action. Twelve-week-old db/db diabetic mice were employed in this study. Systemic use of EPO improved glucose profiles in type 2 diabetic mice after 4 and 8 weeks treatment. EPO up-regulated EPOR protein expression in skeletal muscle, and subsequently activated downstream signaling molecules such as JAK2, IRS-1, PI3K, AKT, and eNOS. We next constructed lentivirally-delivered shRNAs against EPOR and transfected skeletal muscle cells to knockdown EPOR. EPOR knockdown inhibited EPO induced JAK2, IRS-1, PI3K, AKT, eNOS signaling transduction, autophagy and Glut 4 translocation, as well as promoted apoptosis in skeletal muscle. Thus, EPO reduces skeletal muscle IR in type 2 diabetic mice via its specific receptor, EPOR. Possible mechanisms involved in its action may include increased autophagy and reduced apoptosis in type 2 diabetic skeletal muscles, which provides a new strategy for the treatment of IR.


Erythropoietin (EPO); Erythropoietin receptor EPOR; Insulin resistance (IR); Insulin signaling.; Skeletal muscle; type 2 diabetes

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