Article Text


  1. L Mansor,
  2. C Carr,
  3. K Clarke,
  4. L Heather
  1. University of Oxford


    Aims We aim to develop a type 2 diabetic rat model which represents closely the characteristics of the diseased state in type 2 diabetic humans such as hyperglycaemia, hyperinsulinaemia, dyslipidaemia and obesity. We based our model on the type 2 diabetes was proposed by Reed et al 1, which combines high fat diet and streptozotocin (STZ) instead of relying on a genetic manipulation for disease development like many other rat models. We proposed to determine the optimal dose of streptozotocin (STZ) injection and to investigate cardiac-specific abnormalities in this new model of type 2 diabetes, to determine its suitability for studying diabetic cardiomyopathy.

    Methods Male Wistar rats were fed a high fat diet followed by an intraperitoneal injection of STZ at either 15, 20, 25 or 30 mg/kg body weight.

    Results We observed a dose-dependent increase in plasma glucose and non-esterified fatty acids with increasing concentration of STZ. There were dose-independent increases in cardiac and hepatic triglycerides, and decreases in cardiac and hepatic glycogen content in all diabetic rats. With increasing concentrations of STZ there were dose-dependent increases in cardiac UCP3, PDK4 and MCAD protein levels, and decreases in GLUT4 and GLUT1 protein levels. Consequently, the dose of 25 mg/kg STZ was chosen for further metabolic studies. These diabetic rats showed a 39% increase in fasted insulin concentrations and 73% increase in glucose concentrations. Isolated heart perfusion using 3H-glucose demonstrated that both insulin-independent and insulin-stimulated glycolytic rates were decreased by 56% and 43%, respectively, in diabetic hearts compared with controls, in the absence of any change in systolic function.

    Conclusions This demonstrates that high fat feeding combined with 25 mg/kg STZ induces a cardiac metabolic phenotype that resembles that found in type 2 diabetic patients

    Statistics from

    Request permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.