In order to determine if cardiac membrane Ca(2+)-transport activities are 
altered in chronic diabetes induced by alloxan, rats were given an intravenous 
injection of 65 mg/kg and the hearts were used 8 weeks later. Some 4 weeks, 
diabetic animals were injected with insulin (3 U/day) for 4 weeks. Both 
sarcolemmal (SL) and sarcoplasmic reticulum (SR) membranes were isolated from 
the ventricular tissue and their Ca(2+)-transporting activities were determined. 
SL Na(+)-dependent Ca2+ uptake, ATP-dependent Ca2+ uptake and Ca(2+)-stimulated 
ATPase activities were depressed in the diabetic heart. Likewise, SR 
ATP-dependent Ca2+ uptake activity in the diabetic heart was markedly decreased 
in comparison to the control preparations. These defects in diabetic SL and SR 
Ca(2+)-transport activities were prevented by treatment of diabetic animals with 
insulin. The results from the alloxan-rat model of diabetes support the view 
that membrane abnormalities with respect to Ca2+ handling may lead to the 
occurrence of intracellular Ca2+ overload and the development of diabetic 
cardiomyopathy.