Reversibility of diabetic cardiomyopathy with insulin in rats.
Diabetes appears to cause a cardiomyopathy independent of atherosclerotic coronary artery disease and hypertension. Left ventricular papillary muscle function studies in rats made severely diabetic with streptozotocin have shown a slowing of relaxation and a depression of shortening velocity. However, the effects of insulin therapy on the myocardial mechanics of diabetic rats have not been studied. Therefore, rats diabetic for 6-10 weeks were treated with PZI insulin for 2, 6, 10, or 28 days and the mechanical performance of their left ventricular papillary muscles was compared to that of untreated diabetics and age-matched controls; cardiac contractile protein enzymatic activity was also measured. Neither 2 nor 6 days of therapy had any effects on the depressed cardiac muscle performance of diabetic animals, although plasma glucose concentration was restored to normal. By 10 days of therapy, recovery of mechanical performance was nearly complete, and by 28 days of therapy, complete reversal of the altered myocardial mechanics was observed. Crystalline insulin added to the bath (9 mU/ml) had no effect on myocardial mechanics in either diabetics or controls. A gradual recovery of actomyosin and myosin ATPase activity in the hearts of insulin-treated diabetic animals was also found, complementing the mechanical studies. In addition to demonstrating a gradual but complete reversibility of the abnormalities in papillary muscle function in diabetic rats (although control of hyperglycemia was less than ideal), this study confirms that this model of a cardiomyopathy is not a result of streptozotocin-induced cardiac toxicity. Additional data are provided indicating that depressed thyroid hormone levels in diabetic rats are not responsible for the mechanical changes observed.
D000818:Animals; D001786:Blood Glucose; D001835:Body Weight; D009202:Cardiomyopathies / Q000209:etiology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000188:drug therapy; D005260:Female; D007328:Insulin / Q000627:therapeutic use; D009124:Muscle Proteins; D009200:Myocardial Contraction; D010210:Papillary Muscles / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D001786:Blood Glucose; D007328:Insulin; D009124:Muscle Proteins