Next Article in Journal
Methyl Gallate Inhibits Osteoclast Formation and Function by Suppressing Akt and Btk-PLCγ2-Ca2+ Signaling and Prevents Lipopolysaccharide-Induced Bone Loss
Previous Article in Journal
Predictive and Prognostic Molecular Biomarkers for Response to Neoadjuvant Chemoradiation in Rectal Cancer
Previous Article in Special Issue
Metabolic Adaptation in Obesity and Type II Diabetes: Myokines, Adipokines and Hepatokines
Article Menu
Issue 3 (March) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2017, 18(3), 580;

Zinc Prevents the Development of Diabetic Cardiomyopathy in db/db Mice

1,* , 1
1,* and 2,4
Cardiovascular Center & Geriatric Medicine, The First Hospital of Jilin University, Changchun 130021, Jilin, China
Pediatric Research Institute, The Department of Pediatrics, University of Louisville, Louisville, KY 40202, USA
Gynecology and Obstetrics, The Second Hospital of Jilin University, Changchun 130041, Jilin, China
Wendy Novak Diabetes Care Center, Departments of Pharmacology and Toxicology, University of Louisville, Louisville, KY 40202, USA
These authors contributed equally to this work.
Authors to whom correspondence should be addressed.
Academic Editor: Giovanni Tarantino
Received: 27 January 2017 / Revised: 23 February 2017 / Accepted: 26 February 2017 / Published: 7 March 2017
(This article belongs to the Special Issue Diabetic Complications: Pathophysiology, Mechanisms, and Therapies)
Full-Text   |   PDF [4184 KB, uploaded 7 March 2017]   |  


Diabetic cardiomyopathy (DCM) is highly prevalent in type 2 diabetes (T2DM) patients. Zinc is an important essential trace metal, whose deficiency is associated with various chronic ailments, including vascular diseases. We assessed T2DM B6.BKS(D)-Leprdb/J (db/db) mice fed for six months on a normal diet containing three zinc levels (deficient, adequate, and supplemented), to explore the role of zinc in DCM development and progression. Cardiac function, reflected by ejection fraction, was significantly decreased, along with increased left ventricle mass and heart weight to tibial length ratio, in db/db mice. As a molecular cardiac hypertrophy marker, atrial natriuretic peptide levels were also significantly increased. Cardiac dysfunction and hypertrophy were accompanied by significantly increased fibrotic (elevated collagen accumulation as well as transforming growth factor β and connective tissue growth factor levels) and inflammatory (enhanced expression of tumor necrosis factor alpha, interleukin-1β, caspase recruitment domain family member 9, and B-cell lymphoma/leukemia 10, and activated p38 mitogen-activated protein kinase) responses in the heart. All these diabetic effects were exacerbated by zinc deficiency, and not affected by zinc supplementation, respectively. Mechanistically, oxidative stress and damage, mirrored by the accumulation of 3-nitrotyrosine and 4-hydroxy-2-nonenal, was significantly increased along with significantly decreased expression of Nrf2 and its downstream antioxidants (NQO-1 and catalase). This was also exacerbated by zinc deficiency in the db/db mouse heart. These results suggested that zinc deficiency promotes the development and progression of DCM in T2DM db/db mice. The exacerbated effects by zinc deficiency on the heart of db/db mice may be related to further suppression of Nrf2 expression and function. View Full-Text
Keywords: diabetic cardiomyopathy; zinc supplement; nuclear factor-erythroid 2-related factor 2; inflammation; oxidative stress diabetic cardiomyopathy; zinc supplement; nuclear factor-erythroid 2-related factor 2; inflammation; oxidative stress

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Share & Cite This Article

MDPI and ACS Style

Wang, S.; Wang, B.; Wang, Y.; Tong, Q.; Liu, Q.; Sun, J.; Zheng, Y.; Cai, L. Zinc Prevents the Development of Diabetic Cardiomyopathy in db/db Mice. Int. J. Mol. Sci. 2017, 18, 580.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top