Abnormal Myocardial Calcium Uptake in Streptozocin-diabetic Rats: Evidence for a Direct Insulin Effect on Catecholamine Sensitivity

Myocardial calcium uptake after isoproterenol (ISO) in the isolated, perfused heart was investigated at 24-h intervals after the injection of streptozocin (STZ) in rats. After 4 days, when hyperglycemia had persisted for 3 days, myocardial calcium uptake in response to this strong beta-adrenergic agonist fell significantly to the level of unstimulated hearts, which also was the level of propranolol-pretreated hearts exposed to ISO. Insulin, when given in vivo 60-90 min before perfusion, led to a complete normalization of this ISO response in diabetic rats (duration 8 days), while in vitro addition of insulin to the perfusate (0.1 U/ml) significantly increased, while not completely normalizing, the ISO-induced myocardial calcium uptake. Insulin, therefore, has a direct effect on this beta-adrenergic response in diabetic rats and streptozocin in itself does not cause the desensitization. Considering the essential role of this calcium transport for the electromechanical coupling in the heart, such metabolically induced changes in catecholamine sensitivity might hypothetically have relevance for the increased incidence of heart failure in diabetes.