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Cardiac membrane Ca(2+)-transport in alloxan-induced diabetes in rats
L S Golfman1, N Takeda, N S Dhalla
1Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Manitoba, Canada.
Abstract:
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.