Erythropoietin protects against diabetes through direct effects on pancreatic β cells

Diana Choi, Stephanie A. Schroer, Shun Yan Lu, Linyuan Wang, Xiaohong Wu, Yunfeng Liu, Yi Zhang, Herbert Y. Gaisano, Kay Uwe Wagner, Hong Wu, Ravi Retnakaran, Minna Woo

Research output: Contribution to journalArticlepeer-review

118 Scopus citations

Abstract

A common feature among all forms of diabetes mellitus is a functional β-cell mass insufficient to maintain euglycemia; therefore, the promotion of β-cell growth and survival is a fundamental goal for diabetes prevention and treatment. Evidence has suggested that erythropoietin (EPO) exerts cytoprotective effects on nonerythroid cells. However, the influence of EPO on pancreatic β cells and diabetes has not been evaluated to date. In this study, we report that recombinant human EPO treatment can protect against diabetes development in streptozotocin-induced and db/db mouse models of type 1 and type 2 diabetes, respectively. EPO exerts antiapoptotic, proliferative, antiinflammatory, and angiogenic effects within the islets. Using β-cell-specific EPO receptor and JAK2 knockout mice, we show that these effects of EPO result from direct biological effects on β cells and that JAK2 is an essential intracellular mediator. Thus, promotion of EPO signaling in β cells may be a novel therapeutic strategy for diabetes prevention and treatment.

Original languageEnglish (US)
Pages (from-to)2831-2842
Number of pages12
JournalJournal of Experimental Medicine
Volume207
Issue number13
DOIs
StatePublished - Dec 20 2010

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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