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©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Biol Chem. Feb 26, 2015; 6(1): 1-15
Published online Feb 26, 2015. doi: 10.4331/wjbc.v6.i1.1
Published online Feb 26, 2015. doi: 10.4331/wjbc.v6.i1.1
Chronic alcohol consumption potentiates the development of diabetes through pancreatic β-cell dysfunction
Ji Yeon Kim, Dae Yeon Lee, Yoo Jeong Lee, Keon Jae Park, Kyu Hee Kim, Won-Ho Kim, Division of Metabolic Diseases, Center for Biomedical Science, National Institute of Health, Osong-eup, Heungdeok-gu, Cheongju, Chungbuk 363-700, South Korea
Jae Woo Kim, Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul 120-752, South Korea
Author contributions: All authors contributed to this manuscript.
Supported by A grant from the Korean National Institute of Health, No. 4845-302-201-13.
Conflict-of-interest: No potential conflicts of interest relevant to this article were reported.
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: Won-Ho Kim, PhD, Division of Metabolic Diseases, Center for Biomedical Science, National Institute of Health, #187 Osong Saengmyeong2-ro, Osong-eup, Heungdeok-gu, Cheongju, Chungbuk 363-700, South Korea. jhkwh@nih.go.kr
Telephone: +82-43-7198691 Fax: +82-43-7198602
Received: June 29, 2014
Peer-review started: June 29, 2014
First decision: September 18, 2014
Revised: November 19, 2014
Accepted: December 3, 2014
Article in press: December 10, 2014
Published online: February 26, 2015
Processing time: 221 Days and 10.2 Hours
Peer-review started: June 29, 2014
First decision: September 18, 2014
Revised: November 19, 2014
Accepted: December 3, 2014
Article in press: December 10, 2014
Published online: February 26, 2015
Processing time: 221 Days and 10.2 Hours
Core Tip
Core tip: Chronic ethanol consumption induces Glucokinase (GCK) downregulation and inactivation through Tyr nitration, resulting in pancreatic β-cell apoptosis and dysfunction. Additionally, GCK proteins nitrated following ethanol treatment may be more susceptible to ubiquitination and consequent degradation than are native proteins of control cells. Peroxynitrite-mediated GCK downregulation or inactivation may perturb glucose metabolism and cellular antioxidant defense mechanisms, increasing susceptibility to insulin resistance and type-2 diabetes. Furthermore, peroxynitrite-generated activating transcription factor 3 may play as a major upstream regulator of GCK downregulation in β-cell dysfunction and apoptosis.