title: Erythropoietin protects against diabetes through direct effects on pancreatic beta cells.
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.
authors.affiliation: Institute of Medical Science, University of Toronto, Toronto, Ontario M5S 1A1, Canada.
authors.forename: Diana
authors.initials: D
authors.lastname: Choi
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Schroer
authors.forename: Shun Yan
authors.initials: SY
authors.lastname: Lu
authors.forename: Linyuan
authors.initials: L
authors.lastname: Wang
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Wu
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Liu
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Herbert Y
authors.initials: HY
authors.lastname: Gaisano
authors.forename: Kay-Uwe
authors.initials: KU
authors.lastname: Wagner
authors.forename: Hong
authors.initials: H
authors.lastname: Wu
authors.forename: Ravi
authors.initials: R
authors.lastname: Retnakaran
authors.forename: Minna
authors.initials: M
authors.lastname: Woo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control; D004921:Erythropoietin / Q000235:genetics / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017467:Receptors, Erythropoietin / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D001786:Blood Glucose; D007328:Insulin; D019394:Ki-67 Antigen; D017467:Receptors, Erythropoietin; D011994:Recombinant Proteins; D004921:Erythropoietin; D053614:Janus Kinase 2