CHARACTERIZATION OF MYOCARDIAL CONTRACTILE DYSFUNCTION IN TYPE 2 DIABETES MOUSE MODEL

Abstract

CHARACTERIZATION OF MYOCARDIAL CONTRACTILE DYSFUNCTION IN TYPE 2 DIABETES MOUSE MODELEduardo Fricovsky, Sang Ihm, Jorge Suarez, Brian Scott, Francisco Villarreal, , Darrell Belke, Mary O. Oyeleye, Wolfgang DillmannUniversitty of California, San Diego, La Jolla California.Type 2 diabetes mellitus (DMII) contributes to cardiac dysfunction. Characterization of the development of cardiac dysfunction in DMII animal models has been incompletely explored. Currently, it is unknown if cardiac dysfunction occurs in DMII mouse even with mild hyperglycemia and insulin resistance. DMII was induced in mice by feeding a high fat diet (60% fat) and administering a single low dose of streptozotocin (75 mg/Kg). Echocardiography was performed at 2, 4, and 6 months post treatment and diastolic and systolic parameters, as well as biochemical analysis were assessed. Our results show that DMII mice have slightly increased fasting blood glucose compared with control mice (DMII: 124±13 vs. Control: 90±2.0mg/dL). Insulin serum levels were 3 fold increased starting at 2 months in DMII mice suggesting insulin resistance. At 6 months of DMII SERCA2a protein levels was significantly decreased by 50% in hearts. Echo results also showed that at 6 months of DMII mouse hearts already exhibited significant cardiac dysfunction. Fractional Shortening was significantly reduced (DMII: 30.8±6.1% vs. Control: 40.8±4.5%) and LV diastolic (DMII: 3.59±0.16mm vs. Control: 4.03±0.14mm) and systolic (DMII: 2.13±0.2mm vs. Control: 2.79±0.3mm) dimensions were decreased. In conclusion, this data indicates that cardiac dysfunction can develop in DMII mouse hearts even with mild hyperglycemia.