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Effects of insulin or thyroid treatment on diabetes-induced myocardial abnormalities

University of British Columbia

Diabetes induced in female Wistar rats by an intravenous injection of streptozotocin resulted in myocardial changes six weeks after injection of the drug. The left ventricular developed pressure (LVDP), the rate of pressure rise (positive dP/dt) and the rate of pressure decline (negative dP/dt) were depressed in diabetic rat hearts as compared to controls when measured using the working heart technique. The ability of myocardial SR to transport calcium was also depressed in diabetic animals and the level of long chain acylcarnitines was elevated in these animals. Treatment of the diabetic animals with insulin (0.9 U/100g/day) immediately after the disease was detected prevented the deterioration of the physical condition of diabetic animals. The treated animals did not lose weight, had normal plasma glucose and insulin values and the degree of glycosylation of hemoglobin did not differ significantly from controls. Cardiac function as reflected by LVDP and positive and negative dP/dt was not depressed in insulin treated diabetic rats. In parallel to these results, it was found that the level of long chain acylcarnitines in SR of treated animals was not elevated. Calcium uptake activity of SR was also normal in diabetic animals treated with insulin. The data suggest that insulin treatment is capable of preventing changes in the myocardium of diabetic rats. In the next set of experiments, diabetic animals were treated with insulin six weeks after the disease was induced. Four weeks of treatment normalized the physical features i.e. body weight, plasma glucose and plasma insulin values. However, glycosylated hemoglobin values were not completely reversed to normal. Studying the heart function, it was found that such treatment was effective in reversing the depressed cardiac function to normal. Calcium uptake activity and long chain acylcarnitine levels in SR were also reversed to normal. These experiments suggest that insulin treatment is capable of reversing as well as preventing diabetes-induced myocardial alterations. The effect of insulin treatment on hearts of rats from five month diabetic animals was then examined. General features of the five month animals were similar to those described in the ten week reversal study. Heart function analysis revealed that while the LVDP and positive dP/dt were only partially reversed by insulin treatment, negative dP/dt was completely normalized. These studies suggest that the cardiac alterations induced by diabetes can be normalized by insulin if treatment is initiated soon after the onset of diabetes. As diabetes results in hypothyroidism, we studied the effect of thyroid replacement therapy on diabetes-induced alterations. Treatment of diabetic animals with T₃ (30 μg/kg/day) normalized the thyroid status of diabetic animals. However, cardiac function remained depressed in the T₃ treated animals as did the calcium uptake in SR. Thus diabetes-induced myocardial alterations do not seem to be a result of the hypothyroidism. Our study also shows a correlation between the calcium uptake ability of SR and levels of long chain acylcarnitines in SR with myocardial function. The correlationship, however, does not necessarily imply causality.

Text

2010-04-22

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http://hdl.handle.net/2429/24043

Pharmacology

University of British Columbia

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