Effects of diabetes mellitus and aluminum toxicity on myocardial calcium transport.
Diabetics have an increased risk of developing renal insufficiency, as well as congestive heart failure independent of coronary atherosclerotic or hypertensive heart disease. Aluminum toxicity is being recognized with increased frequency in patients with reduced renal function and aluminum accumulates to a greater degree in tissues of patients with diabetes. Studies in patients with end stage renal disease have implicated aluminum overload as a potential cause of reduced cardiac function. Since both diabetes and aluminum decrease the activity of (Ca + Mg)-ATPase, a key enzyme involved in myocardial calcium transport, the interaction of experimental diabetes mellitus and aluminum toxicity on myocardial sarcoplasmic reticulum calcium transport was investigated in rats. Aluminum alone had no effect on (Ca + Mg)-ATPase activity, while activities in both the diabetic ([DM]) and diabetic plus aluminum loaded ([DM + Al]) groups were significantly lower than controls ([C]). Oxalate-dependent calcium uptake in the [DM] rats was slightly, but not significantly lower than controls, however, uptake was markedly reduced in rats which were both diabetic and aluminum loaded. The calcium regulatory protein calmodulin was measured by a functional assay in the soluble fraction of myocardial tissue prepared from each of the four groups. Compared to [C], calmodulin activity was significantly reduced in both the [DM] and [DM + Al] groups but not affected by aluminum alone. These data indicate that diabetes mellitus is associated with decreased myocardial calmodulin activity that may contribute to reduced sarcoplasmic reticulum (Ca + Mg)-ATPase and calcium transport activities and that aluminium toxicity potentiates the adverse effects of diabetes on decreasing sarcoplasmic reticulum calcium uptake.
Levine
S N
SN
Department of Medicine, Louisiana State University Medical Center, Shreveport 71130.
Sonnier
G B
GB
Abreo
K
K
D000255:Adenosine Triphosphate / Q000378:metabolism; D000535:Aluminum / Q000633:toxicity*; D000818:Animals; D001692:Biological Transport; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D002846:Chromatography, Affinity; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D006442:Glycated Hemoglobin / Q000032:analysis; D006321:Heart / Q000187:drug effects*; D008297:Male; D008861:Microsomes / Q000201:enzymology / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism*; D009929:Organ Size; D051381:Rats; D011919:Rats, Inbred Strains; D012519:Sarcoplasmic Reticulum / Q000378:metabolism
D000255:Adenosine Triphosphate; D000535:Aluminum; D001786:Blood Glucose; D017301:Ca(2+) Mg(2+)-ATPase; D002118:Calcium; D000252:Calcium-Transporting ATPases; D002147:Calmodulin; D006442:Glycated Hemoglobin