Abstract
Diabetic cardiomyopathy is a prominent cause of heart failure in patients with diabetes mellitus. Currently, there is no specific treatment for diabetic cardiomyopathy. This study aimed to investigate the effect and underlying mechanisms of Zinc (Zn) supplementation in the protection against diabetic cardiomyopathy in a rat model of type 2 diabetes mellitus (T2DM). T2DM-like lesions in male Wistar rats were induced by introducing the high-fat diet and by administration of streptozocin (STZ). After STZ induction, animals with fasting plasma glucose level ≥16.7 mM were considered as diabetic, and randomly assigned to the group receiving physiological saline (control) or ZnSO4 for 56 days. On days 0, 7, 28 and 56 of treatment, animals were weighed, and their blood samples were analyzed. On day 56, hemodynamic assessment was performed right before the sacrifice of animals. Cardiac tissue specimens were collected and subjected to pathologic assessment, metallothionein (MT) concentration measurement and Western blot analysis of microtubule-associated protein light chain 3 (LC3), the marker of autophagy, and glucose-regulated protein-78 (GRP78), an oxidative stress marker. High-fat diet feeding followed by STZ administration resulted in weight loss, hyperglycemia, polydipsia, polyphagia, hemodynamic anomalies and a significant increase in the myocardial content of LC3 and GRP78 proteins, but not in MT protein. Zn supplementation effectively attenuated all these aberrations induced by high-fat diet and STZ. These findings suggest that Zn might be a protective factor in diabetic cardiomyopathy, acting in two ways: at least partially, through inhibiting autophagy and by endoplasmic reticulum stress.
Highlights
Diabetes mellitus (DM) is one of the most common non-communicable diseases, and its prevalence has been increasing rapidly in both developed and developing countries [1]
On day 0, there was no significant difference in body weight among three groups (p>0.05)
Diabetes induction with STZ following high-fat diet feeding resulted in a body weight reduction that was significant on day 7 and sustained through experimental days 28 to 56 (p
Summary
Diabetes mellitus (DM) is one of the most common non-communicable diseases, and its prevalence has been increasing rapidly in both developed and developing countries [1]. Based on the latest information published on the website of the International Diabetes Federation, China has overtaken India and become the leading country in terms of diabetes prevalence. Defined as the presence of functional and structural abnormalities in the absence of coronary artery disease, hypertension and significant valvular disease [3, 4], diabetic cardiomyopathy manifests initially as asymptomatic diastolic dysfunction that eventually progresses to symptomatic heart failure. Echocardiography-based studies showed that 30% of type 2 diabetic patients had diastolic dysfunction [5, 6]. Recent studies using more rigorous and more sensitive Doppler methods showed that over 50% of type 2 diabetic patients had mild and early diastolic dysfunction [7,8]. The pathophysiology of diabetic cardiomyopathy is not completely understood, and it appears to be multifactorial involving hyperglycemia, hyperinsulinemia, abnormal fatty acid metabolism and oxidative stress, cardiac autonomic neuropathy and the local renin-angiotensin-aldosterone system overactivation [9]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
