An Attempt To Reverse Diabetic Cardiomyopathy By Aerobic Interval Training In High-fat Diet And Streptozotocin Induced Type 2 Diabetes Rat Models

Abstract

PURPOSE: Diabetes mellitus (DM) is an important risk factors of cardiovascular disease. Long-term hyperglycemia, hyperlipemia and insulin resistance may lead to diabetic cardiomyopathy (DCM). No rodent models fully captured the whole process of cardiac morphology and function changes during the course of DCM. Aerobic interval training (AIT) has been advised as a non-pharmacological strategy against DM patients. However, little is known whether impose AIT intervention at the onset of DM will reverse the process of DCM. In this study, we sought to evaluate the cardiac function during the development of DCM and explore whether AIT will reverse the process of DCM. METHODS: 60 Wistar male rats were randomly divided into control group (CON), DCM group (DCM) and AIT intervention group (AIT). Rats in DCM group and AIT group used high fat diet and STZ to induce diabetes models. Rats in AIT group were subjected to 8 weeks AIT intervention Fasting blood glucose (FBG), lipid profiles, insulin resistance (IR) and GLP-1 levels was measured. HE staining and echocardiography were used to identify cardiac morphology and function. α-MHC and β-MHC gene expression were detected by RT-PCR. GLP-1 and GLP-1R expression were detected by western blotting. RESULTS: Compared with CON, the heart function of DCM gradually changes from impaired diastolic function to impaired systolic function,with heart developed hypertrophy at onset and gradually cardiac walls became thinner with large LV volume. The FBG, TG and LDL-c levels in AIT was 16.8%, 45.6% and 74.7% lower than that in DCM (P<0.01). AIT increased HDL-c level up to 60% than DCM (P<0.01). AIT significantly decreased IR for 37.3% (P<0.01). Histological analysis and echocardiography results revealed that AIT prevent the thinners of cardiac wall and improve systolic and diastolic function. There is a 81% increase of α-MHC mRNA expression and a 67% decrease of β-MHC mRNA expression in AIT group than in DCM (P<0.01), which represented that AIT prevent the heart transformation to embryo type. AIT protect DCM heart through improving serum GLP-1 level (80%, P<0.05) , heart GLP-1 expression (144%, P<0.01) and GLP-1R expression (219%, P<0.01). CONCLUSIONS: AIT intervention may reverse the process of DCM by activating of GLP-1/GLP-1R signaling.