TY - JOUR
T1 - Erythropoietin protects against diabetes through direct effects on pancreatic β cells
AU - Choi, Diana
AU - Schroer, Stephanie A.
AU - Lu, Shun Yan
AU - Wang, Linyuan
AU - Wu, Xiaohong
AU - Liu, Yunfeng
AU - Zhang, Yi
AU - Gaisano, Herbert Y.
AU - Wagner, Kay Uwe
AU - Wu, Hong
AU - Retnakaran, Ravi
AU - Woo, Minna
PY - 2010/12/20
Y1 - 2010/12/20
N2 - 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.
AB - 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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U2 - 10.1084/jem.20100665
DO - 10.1084/jem.20100665
M3 - Article
C2 - 21149549
AN - SCOPUS:78650397022
SN - 0022-1007
VL - 207
SP - 2831
EP - 2842
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 13
ER -