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Am J Physiol Endocrinol Metab 257: E573-E577, 1989;
0193-1849/89 $5.00
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AJP - Endocrinology and Metabolism, Vol 257, Issue 4 E573-E577, Copyright © 1989 by American Physiological Society


ARTICLES

Diabetes decreases creatine kinase enzyme activity and mRNA level in the rat heart

B. K. Popovich, K. R. Boheler and W. H. Dillmann
Department of Medicine, University of California, San Diego 92103.

Several of the adenosinetriphosphatase enzymes that are responsible for cardiac muscle contraction rely on high-energy phosphates supplied by the creatine kinase (CK) system. Experimental diabetes mellitus has been shown to cause a decrease in the maximal contractile performance of the heart. We postulated that the decrease in contractile performance may be explained in part by a decrease in CK enzyme activity. To evaluate this possibility, we determined the level of CK activity and isoenzyme distribution in ventricular homogenates from normal, diabetic, and insulin-treated diabetic rats. We found that total CK activity was decreased by 35% in diabetic hearts and that a 66% reduction in the cardiac-specific MB isoenzyme occurs. Using a cDNA probe for CK-muscle (M) RNA in Northern blot analysis, we determined that a 61.1% decrease in CK-M mRNA occurs in diabetes. Chronic insulin therapy for 1 mo restores CK-M mRNA levels and enzyme activity. In conclusion, diabetes-induced CK enzyme decreases are mediated in part by a lower level of CK-M mRNA that codes for the major CK-M subunit protein. Decreased performance of the CK system may contribute to diabetic cardiomyopathy.


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[Abstract] [Full Text] [PDF]




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