Endurance Exercise Prevented Diabetic Cardiomyopathy through the Inhibition of Fibrosis and Hypertrophy in Rats.

Background: Exercise training could be essential in preventing pathological cardiac remodeling in diabetes. Therefore, the effects of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) singly or plus metformin on diabetes-induced cardiomyopathy were investigated in this study. Methods: Forty-nine Wistar rats (male) were recruited. Seven groups of animals were treated for six weeks as control, diabetes, MICT (15 m/min, 40 min/day), HIIT (20 m/min, 40 min/day), metformin (300 mg/kg), HIIT+metformin (Met-HIIT), and MICT+metformin (Met-MICT). The metformin was orally administered with an intragastrical needle, and the exercised rats were trained (5 days/week) with a motorized treadmill. Metabolic parameters, echocardiographic indices, histopathology evaluation, and assessment of gene expression connected with cardiac fibrosis, hypertrophy, mitochondrial performance, and intracellular calcium homeostasis were investigated. Results: Our results demonstrated that all the interventions prevented weight loss and enhanced heart weight/body weight ratio and fasting plasma glucose in diabetic rats. Both types of exercise and their metformin combinations improved diabetic animals' echocardiography indices by enhancing heart rate, fractional shortening (FS), ejection fraction (EF) and reducing end-systolic and end-diastolic diameter of left ventricular (LVESD and LVEDD). Gene expression of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), transforming growth factor (TGF)- ß , and collagen increased in the diabetes group. In contrast, the gene expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 α ), AMP-activated protein kinase (AMPK), ryanodine receptors (RyR), and Ca 2 + ATPase pump of the sarcoplasmic reticulum (SERCA) was reduced in diabetic animals. Exercise training alone or in combination with metformin reversed these changes. Moreover, diabetes-induced cardiac fibrosis was ameliorated in treated groups. All indicators of diabetic cardiomyopathy were improved more in the Met-HIIT group than in other groups. Conclusions: Exercise training, notably with metformin combination, alleviated diabetes-induced cardiac complications. The beneficial effects of exercise could be related to improving pathological cardiac remodeling and enhancing cardiac function.

Cardiac hypertrophy and fibrosis were attenuated by olive leaf extract treatment in a rat model of diabetes.

The key role of fibrosis and hypertrophy processes in developing diabetes-induced heart injury has been demonstrated. Considering the known hypoglycemic effects of olive leaf extract (OLE), we decided to investigate its potential effect and associated mechanisms on cardiac fibrosis and myocardial hypertrophy in streptozotocin (STZ)-induced diabetic rats. Eight groups were included in this study: control, diabetic, diabetic-OLEs (100, 200 and 400 mg/kg), diabetic-metformin (300 mg/kg), diabetic-valsartan (30 mg/kg), and diabetic-metformin/valsartan (300/30 mg/kg). After a treatment period of 6 weeks, echocardiography was used to assess cardiac function. Heart-to-body weight ratio (HW/BW) and fasting blood sugar (FBS) were measured. Myocardial histology was examined by Masson's trichrome staining. Gene expressions of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), ß-myosin heavy chain (ß-MHC), TGF-ß1, TGF-ß3, angiotensin II type 1 receptor (AT1), alpha-smooth muscle actin (α-SMA), and collagen were evaluated by the quantitative real-time PCR in heart tissue. A reduction in the FBS level and HW/BW ratio in the extract groups was obvious. The improvement of left ventricular dysfunction, cardiac myocytes hypertrophy, and myocardial interstitial fibrosis was also observed in treated groups. A lowering trend in the expression of all hypertrophic and fibrotic indicator genes was evident in the myocardium of OLE treated rats. Our data indicated that OLE could attenuate fibrosis and reduce myocardial hypertrophy markers, thus improving the cardiac function and structure in the STZ-induced diabetic rats. PRACTICAL APPLICATIONS: This study demonstrates that olive leaf extract in addition to lowering blood glucose levels and the heart-to-body weight ratio (HW/BW) may also improve cardiac function and reduce cardiac hypertrophy and fibrosis in cardiac tissue, which leads to inhibition of diabetic heart damage. Thus it is possible that including olive leaf extracts in the diets of individuals with diabetes may assist in lowering cardiovascular disease risk factors.