Hexose transport modification of rat hearts during development of chronic diabetes

Transport of 3-o-methylglucose into hearts of chronic diabetic rats was studied to determine if loss of transporter activity could be accounted for by higher concentrations of citrate and triglyceride and to determine if 7 days post alloxan was a representative time period for study of myocardial changes in chronic diabetes. Chronic diabetes was induced in rats by rapid i.v. injection of alloxan (37.5 mg/kg body weight), and the rats were studied 1 to 5 weeks afterward. Basal sugar transport rate in isolated perfused hearts declined after 2 weeks of diabetes and was nearly undetectable at 3 to 5 weeks. Stimulation of transport by insulin was also very low. Triglyceride concentrations were 50% of normal and G6P concentrations were elevated, but citrate concentrations were not different from control. Results of these studies showed that tissue triglyceride and citrate concentrations were not correlated with transport inhibition in chronic diabetic rat hearts. Loss of basal transport activity and lowered insulin sensitivity in these hearts is more likely due to a loss of transporters from the sarcolemma. These studies also show that transport rate and metabolite concentrations continue to change over 5 weeks of diabetes, and, therefore, one time point cannot be defined as representative of chronic diabetes.