Abstract
Increasing evidence shows that diabetes causes cardiac dysfunction. We hypothesized that a glucagon-like peptide-1 (GLP-1) analog, liraglutide, would attenuate cardiac dysfunction in diabetic rats. A total of 24 Sprague–Dawley (SD) rats were divided into two groups fed either a normal diet (normal, n=6) or a high-fat diet (HFD, n=18) for 4 weeks. Then, the HFD rats were injected with streptozotocin (STZ) to create a diabetic rat model. Diabetic rats were divided into three subgroups receiving vehicle (diabetic, n=6), a low dose of liraglutide (Llirag, 0.2 mg/kg/day, n=6), or a high dose of liraglutide (Hlirag, 0.4 mg/kg/day, n=6). Metabolic parameters, systolic blood pressure (SBP), heart rate (HR), left ventricular (LV) function, and whole genome expression of the heart were determined. Diabetic rats developed insulin resistance, increased blood lipid levels and oxidative stress, and impaired LV function, serum adiponectin, nitric oxide (NO). Liraglutide improved insulin resistance, serum adiponectin, NO, HR, and LV function and reduced blood triglyceride (TG), total cholesterol (TC) levels, and oxidative stress. Moreover, liraglutide increased heart nuclear receptor subfamily 1, group H, member 3 (Nr1h3), peroxisome proliferator activated receptor (Ppar) α (Pparα), and Srebp expression and reduced diacylglycerol O-acyltransferase 1 (Dgat) and angiopoietin-like 3 (Angptl3) expression. Liraglutide prevented cardiac dysfunction by activating the PPARα pathway to inhibit Dgat expression and oxidative stress in diabetic rats.
Highlights
Diabetes is a worldwide public health problem that has prevalence greater than 5.71% in adults [1]
Liraglutide treatment decreased systolic blood pressure (SBP), heart rate (HR), LV end-diastolic diameter (LVEDD), and LV end-systolic diameter (LVESD) levels and increased % Fractional shortening (FS) values (P
We found that liraglutide reduced SBP, HR, LVEDD, and LVESD levels, increased %FS values and serum nitric oxide (NO) levels in diabetic rats
Summary
Diabetes is a worldwide public health problem that has prevalence greater than 5.71% in adults [1]. Chronic hyperglycemia leads to a high risk of cardiovascular events [2]. Cardiovascular disease is a leading cause of morbidity and mortality worldwide. Diabetic cardiomyopathy (DCM) is defined as cardiac hypertrophy that is independent of hypertension and coronary artery disease (CAD). The three main risk factors of DCM are insulin resistance, hyperinsulinemia, and hyperglycemia. Some cellular and molecular defects, including impaired insulin signaling, hyperglycemia, glucotoxicity, cardiac lipotoxity, mitochondrial dysfunction, oxidative stress, endoplasmic reticulum (ER) stress, and cardiomyocyte apoptosis, have been reported as primary causes of DCM pathogenesis [3,4]. Treatments providing glycemic control and cardiovascular protection are important to improve the health of people all over the world [5]
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