Conference Proceedings (Biomedical Science Research Day)

Abstract

Introduction: Diabetes mellitus is a serious global health problem and cardiovascular complications are the major cause of morbidity and mortality in diabetic patients. The Goto-Kakizaki (GK) rat is a genetic model of type 2 diabetes derived from an outbred colony of Wistar stock by selective breeding for the highest blood glucose levels during an oral glucose tolerance test. Several studies have investigated the effects of diabetes mellitus on heart function in GK rat. These studies have variously reported alterations in time course of myocyte shortening, amplitude of intracellular Ca2+ and myofilament sensitivity to Ca2+. High fat diet is a well known added risk factor for cardiac complications. Aims & Objectives: Given the clinical prevalence of type 2 diabetes and obesity and their association with high mortality linked to cardiovascular disease the aim of the study was to investigate the effects of feeding type 2 diabetic GK rats either high or low fat diets on ventricular myocyte function. Materials & Methods: GK rats were fed either a high fat diet (HFD) or a low fat diet (LFD) from the age of 2 months for a period of 7 months. Experiments were performed when the animals were 9 months of age. Ventricular myocytes were isolated by enzymatic and mechanical dispersal techniques. Myocyte shortening was measured with a video detection system and intracellular Ca2+ was measured in fura-2 loaded cells by fluorescence photometry. Results & Discussion: At 7 months the non-fasting blood glucose was higher in GK rats fed LFD (334±35 mg/dl) compared to GK rats fed HFD (235±26 mg/dl) rats. Feeding GK rats with a HFD had no significant effect on blood glucose clearance following a glucose challenge. Time to peak (TPK) shortening was reduced in myocytes from GK rats fed HFD (131.8±2.1 ms) compared to GK rats fed LFD (144.5±3.0 ms) and time to half (THALF) relaxation of shortening was also reduced in myocytes from GK rats fed HFD 71.7±6.9 ms) compared to GK rats fed LFD (86.1±3.6 ms). HFD had no significant effect on the amplitude of shortening. HFD had no significant effect on TPK, THALF decay, amplitude of the Ca2+ transient, myofilament ensitivity to Ca2+, sarcoplasmic reticulum Ca2+ content, fractional release of Ca2+ and the rate of Ca2+ uptake. Conclusion: Time course of shortening and relaxation were reduced in myocytes from GK rats fed a HFD. Changes in intracellular Ca2+ transport do not appear to underlie changes in contractile function.