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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Oct 25, 2015; 6(14): 1259-1273
Published online Oct 25, 2015. doi: 10.4239/wjd.v6.i14.1259
Erythropoietin and diabetes mellitus
Kenneth Maiese
Kenneth Maiese, Cellular and Molecular Signaling, Newark, NJ 07101, United States
Author contributions: Maiese K conceived, designed and wrote this article.
Supported by American Diabetes Association; American Heart Association; NIH NIEHS; NIH NIA; NIH NINDS; and NIH ARRA (to Maiese K).
Conflict-of-interest statement: The author declares no conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Kenneth Maiese, MD, Cellular and Molecular Signaling, 125 Main Street, Newark, NJ 07101, United States. wntin75@yahoo.com
Received: June 10, 2015
Peer-review started: June 11, 2015
First decision: August 16, 2015
Revised: August 25, 2015
Accepted: September 25, 2015
Article in press: September 28, 2015
Published online: October 25, 2015
Processing time: 137 Days and 11.9 Hours
Abstract

Erythropoietin (EPO) is a 30.4 kDa growth factor and cytokine that governs cell proliferation, immune modulation, metabolic homeostasis, vascular function, and cytoprotection. EPO is under investigation for the treatment of variety of diseases, but appears especially suited for the treatment of disorders of metabolism that include diabetes mellitus (DM). DM and the complications of this disease impact a significant portion of the global population leading to disability and death with currently limited therapeutic options. In addition to its utility for the treatment of anemia, EPO can improve cardiac function, reduce fatigue, and improve cognition in patients with DM as well as regulate cellular energy metabolism, obesity, tissue repair and regeneration, apoptosis, and autophagy in experimental models of DM. Yet, EPO can have adverse effects that involve the vasculature system and unchecked cellular proliferation. Critical to the cytoprotective capacity and the potential for a positive clinical outcome with EPO are the control of signal transduction pathways that include protein kinase B, the mechanistic target of rapamycin, Wnt signaling, mammalian forkhead transcription factors of the O class, silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae), and AMP activated protein kinase. Therapeutic strategies that can specifically target and control EPO and its signaling pathways hold great promise for the development of new and effective clinical treatments for DM and the complications of this disorder.

Keywords: Protein kinase B; AMP activated protein kinase; Apoptosis; Autophagy; Forkhead; Metabolism; Factors of the O class; Diabetes mellitus; Erythropoietin; Stem cells; Silent mating type information regulation 2 homolog 1; Oxidative stress; Wnt1 inducible signaling pathway protein 1; Wnt

Core tip: Erythropoietin and the downstream signaling pathways of this cytokine that include protein kinase B, mechanistic target of rapamycin, Wnt signaling, Factors of the O class proteins, silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae), and AMP activated protein kinase offer new avenues for the development of novel treatments for diabetes mellitus and the complications of this disease.