Erythropoietin protects against diabetes through direct effects on pancreatic beta cells.
Erythropoietin protects against diabetes through direct effects on pancreatic beta cells.
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DOI：
10.1084/jem.20100665
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发表时间：
2010-12-20
期刊：
影响因子：
--
通讯作者：
Woo M
中科院分区：
文献类型：
--
作者：
Choi D;Schroer SA;Lu SY;Wang L;Wu X;Liu Y;Zhang Y;Gaisano HY;Wagner KU;Wu H;Retnakaran R;Woo M
In mouse models of type 1 and type 2 diabetes, administration of human erythropoietin protects against disease by acting directly on pancreatic β cells. 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.
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