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Am J Physiol Heart Circ Physiol 276: H1811-H1817, 1999;
0363-6135/99 $5.00
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Vol. 276, Issue 6, H1811-H1817, June 1999

Cardiac myofibrillar and sarcoplasmic reticulum function are not depressed in insulin-resistant JCR:LA-cp rats

Tarun Misra1,3, James S. C. Gilchrist1,2, James C. Russell4, and Grant N. Pierce1,3

1 Division of Stroke and Vascular Disease, St. Boniface General Hospital Research Centre, and Departments of 2 Oral Biology and 3 Physiology, University of Manitoba, Winnipeg, Manitoba R2H 2A6; and 4 Department of Surgery, University of Alberta, Edmonton, Alberta, Canada T6G 2S2

Depressed myofibrillar Ca2+-ATPase activity and sarcoplasmic reticulum (SR) Ca2+ uptake are important mechanisms that are responsible for the cardiac dysfunction exhibited by insulin-deficient (type I) diabetic animals. The JCR:LA-cp rat is a model for type II non-insulin-dependent diabetes mellitus (NIDDM). This rat is insulin resistant, obese, and has high levels of circulating glucose, cholesterol, insulin, and triglycerides. The purpose of this study was to determine whether changes in cardiac myofibrillar, SR, and cardiomyocyte function exist in this model of type II diabetes. Myofibrils and SR were isolated from hearts by differential centrifugation. Surprisingly, we found that myofibrillar Ca2+-ATPase activities were unaltered in these animals. Ca2+ uptake in isolated SR fractions was increased in diabetic cp/cp rats, whereas Ca2+-ATPase activity and ryanodine binding were unchanged. Cardiomyocytes isolated from hearts of control and experimental animals had similar active cell shortening and intracellular Ca2+ concentration under basal conditions and in response to caffeine. Our data argue against the presence of a cardiomyopathy in this diabetic model and suggest that insulin may be an important factor in the cardiomyopathy observed in type I diabetic models.

contractile proteins; calcium; diabetic cardiomyopathy; excitation-contraction coupling; myosin; cardiomyocytes; non-insulin-dependent diabetes mellitus; insulin


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