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J Exp Med. 2010 Dec 20;207(13):2831-42. doi: 10.1084/jem.20100665. Epub 2010 Dec 13.

Erythropoietin protects against diabetes through direct effects on pancreatic beta cells.

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  • 1Institute of Medical Science, University of Toronto, Toronto, Ontario M5S 1A1, Canada.

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.

PMID:
21149549
[PubMed - indexed for MEDLINE]
PMCID:
PMC3005231
Free PMC Article
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