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Modification of myosin isozymes and SR Ca2+-pump ATPase of the diabetic rat heart by lipid-lowering interventions

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Abstract

To define metabolic influences on cardiac myosin expression and sarcoplasmic reticulum (SR) Ca2+-stimulated ATPase streptozotocin-diabetic rats were treated for 9–10 wk with etomoxir, an inhibitor of carnitine palmitoyl transferase I (CPT-1) and fatty acid synthesis, or an antilipolytic drug, acipimox. Etomoxir reduced myosin V3 of diabetic rats but did not normalize it. However, the high serum triglyceride, free-fatty acid and cholesterol concentrations in diabetic animals were greatly reduced. After bypassing the CPT-1 inhibition with a medium-chain fatty acid (miglyol) diet, the V3 contents and serum lipids were still reduced in the etomoxir-treated diabetic rats; V3 was also reduced in diabetic rats fed miglyol or treated with acipimox. Since low serum insulin or triiodothyronine concentrations in diabetic rats were not improved by these interventions but changes in V3 were correlated with those in triglyceride, free-fatty acid and cholesterol concentrations, it is likely that myosin may be influenced by some metabolic factors. To assess the role of adrenergic influences, diabetic rats (7–8 wk) were treated with an antisympathotonic drug, moxonidine, a β-adrenoceptor blocking drug, propranolol, and a bradycardic drug, tedisamil. Myosin V3 was not reduced significantly in moxonidine-treated or propranolol-treated rats in comparison to untreated diabetic rats. Serum thyroid hormones and insulin were not altered, whereas triglycerides were reduced but not significantly by these antiadrenergic agents. Lowering serum lipids in diabetic rats by treatment with etomoxir, miglyol and acipimox increased the depressed SR Ca2+-stimulated ATPase activity. On the other hand, in diabetic rats treated with moxonidine, propranolol or tedisamil, the ATPase activity was not increased significantly. These results suggest that normalization of blood lipids is important for improving subcellular organelle function in diabetic hearts with impaired glucose utilization.

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Authors and Affiliations

  1. Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, 351 Tache Avenue, R2H 2A6, Winnipeg, Canada

    Heinz Rupp, Vijayan Elimban & Naranjan S. Dhalla

  2. Department of Physiology, Faculty of Medicine, University of Manitoba, R2H 2A6, Winnipeg, Canada

    Heinz Rupp, Vijayan Elimban & Naranjan S. Dhalla

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  1. Heinz Rupp
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  2. Vijayan Elimban
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  3. Naranjan S. Dhalla
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Rupp, H., Elimban, V. & Dhalla, N.S. Modification of myosin isozymes and SR Ca2+-pump ATPase of the diabetic rat heart by lipid-lowering interventions. Mol Cell Biochem 132, 69–80 (1994). https://doi.org/10.1007/BF00925676

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  • DOI: https://doi.org/10.1007/BF00925676

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