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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Apoptosis / drug effects*
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Blood Glucose / metabolism
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Blotting, Western
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Cell Proliferation / drug effects
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Diabetes Mellitus, Experimental / genetics
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Diabetes Mellitus, Experimental / metabolism
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Diabetes Mellitus, Experimental / prevention & control*
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Diabetes Mellitus, Type 1 / genetics
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Diabetes Mellitus, Type 1 / metabolism
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Diabetes Mellitus, Type 1 / prevention & control
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Diabetes Mellitus, Type 2 / genetics
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Diabetes Mellitus, Type 2 / metabolism
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Diabetes Mellitus, Type 2 / prevention & control
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Erythropoietin / genetics
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Erythropoietin / pharmacology*
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Female
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Gene Expression Regulation / drug effects
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Humans
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Immunohistochemistry
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Insulin / metabolism
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Insulin-Secreting Cells / drug effects*
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Insulin-Secreting Cells / metabolism
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Janus Kinase 2 / genetics
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Janus Kinase 2 / metabolism
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Ki-67 Antigen / metabolism
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Receptors, Erythropoietin / genetics
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Receptors, Erythropoietin / metabolism
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Recombinant Proteins / pharmacology
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Reverse Transcriptase Polymerase Chain Reaction
Substances
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Blood Glucose
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Insulin
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Ki-67 Antigen
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Receptors, Erythropoietin
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Recombinant Proteins
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Erythropoietin
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Janus Kinase 2