Diabetes decreases creatine kinase enzyme activity and mRNA level in the rat heart.
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.
Popovich
B K
BK
Department of Medicine, University of California, San Diego 92103.
Boheler
K R
KR
Dillmann
W H
WH
D000818:Animals; D015152:Blotting, Northern; D003402:Creatine Kinase / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000235:genetics; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000201:enzymology*; D007328:Insulin / Q000627:therapeutic use; D007527:Isoenzymes; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D007328:Insulin; D007527:Isoenzymes; D012333:RNA, Messenger; D004247:DNA; D003402:Creatine Kinase