Alterations in membrane phospholipids of cardiac sarcoplasmic reticulum in streptozotocin-induced diabetic rats and reversibility by insulin treatment Y. Umezawa, K. Umetsu, Y. Suwa, E. Geshi, N. Konno, M. Yaida, T. Katagiri. Third Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan

Cardiac sarcoplasmic reticulum (SR) function and SR levels of long-chain (LC) acylcarnitines were determined in streptozotocin-induced diabetic rats treated with insulin or D,L-carnitine. ATP-dependent calcium transport was significantly depressed in cardiac SR isolated from untreated diabetic rats compared with control rats. Diabetic rat cardiac SR levels of LC acylcarnitines were also significantly elevated. Various parameters of heart function (left ventricular developed pressure, +dP/dT, and -dP/dT), as determined on an isolated working heart apparatus, were found to be depressed in untreated diabetic rats. Cardiac SR isolated from diabetic rats treated throughout the study period with insulin or D,L-carnitine did not have elevated levels of LC acylcarnitines associated with SR membrane nor was SR calcium transport activity depressed. Heart function in the diabetic rats treated with insulin was similar to control rat hearts but heart function remained depressed in diabetic rats treated with D,L-carnitine. The data suggest that the LC acylcarnitines are involved in the observed impairment of cardiac SR function in diabetic rats. Other factors, however, must be contributing to the depression in heart function noted in these animals.

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The effect of alloxan- and streptozotocin-induced diabetes on calcium transport in rat cardiac sarcoplasmic reticulum. The possible involvement of long chain acylcarnitines

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y83-068 ◽

1983 ◽

Vol 61 (5) ◽

pp. 439-448 ◽

Cited By ~ 66

Author(s):

Gary D. Lopaschuk ◽

Sidney Katz ◽

John H. McNeill

Keyword(s):

Sarcoplasmic Reticulum ◽

Heart Function ◽

Diabetic Rats ◽

Diabetic Rat ◽

Microsomal Preparation ◽

Cardiac Sarcoplasmic Reticulum ◽

Gradual Onset ◽

Female Wistar Rats ◽

Streptozotocin Induced Diabetes ◽

Long Chain

Isolated working hearts from diabetic rats have a decreased ability to respond to increasing preload or afterload. The ability of cardiac sarcoplasmic reticulum to transport Ca2+ was examined in diabetic rats. Hearts were obtained from female Wistar rats 120 days or 7 days after the induction of diabetes by a single I.V. injection of either alloxan (65 mg/kg) or streptozotocin (60 mg/kg). At all Ca2+ concentrations tested (0.2–5.0 μM free Ca2+) cardiac sarcoplasmic reticulum from 120-day diabetic rats showed a significant decrease in the rate of ATP-dependent tris-oxalate facilitated Ca2+ transport (62–73% of control). This was accompanied by a decrease in Ca2+ ATPase activity. The levels of long chain acylcarnitines associated with the microsomal sarcoplasmic reticulum preparation from 120-day diabetic rats were significantly higher than those present in sarcoplasmic reticulum from control rats. Palmitylcarnitine, the most abundant of the long chain acylcarnitines, in concentrations < 7 μM was found to be a potent time-dependent inhibitor of Ca2+ transport in both control and diabetic rat sarcoplasmic reticulum preparations; inhibition of Ca2+ transport was found to be more marked in the control preparations. This would indicate that a degree of inhibition produced by the high endogenous levels of palmitylcarnitine may already be present in the diabetic rat preparations. Cardiac sarcoplasmic reticulum prepared from acutely diabetic rats (7 days) did not show any decrease in Ca2+ transport ability. Levels of long chain acylcarnitines associated with the microsomal preparation enriched in sarcoplasmic reticulum were also unchanged. These findings suggest that the alteration in heart function in 120-day diabetic rats may be due to the buildup of cellular long chain acylcarnitines which inhibit sarcoplasmic reticulum Ca2+ transport. The absence of any change in Ca2+-transport activity or levels of long chain acylcarnitines at 7 days suggests that the alterations seen in 120-day diabetic rats must be of gradual onset.

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