Erythropoietin protects against diabetes through direct effects on pancreatic β cells

Author:

Choi Diana11,Schroer Stephanie A.1,Lu Shun Yan1,Wang Linyuan11,Wu Xiaohong1,Liu Yunfeng11,Zhang Yi11,Gaisano Herbert Y.11,Wagner Kay-Uwe22,Wu Hong3,Retnakaran Ravi1114,Woo Minna11111

Affiliation:

1. Institute of Medical Science, Ontario Cancer Institute, Department of Medical Biophysics, Division of Endocrinology and Metabolism, Department of Medicine; and Department of Physiology, University of Toronto, Toronto, Ontario M5S 1A1, Canada

2. Eppley Institute for Research in Cancer and Allied Diseases and Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198

3. Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095

4. Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario M5T 3L9, 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.

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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