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

Am J Physiol. 1989 Oct;257(4 Pt 1):E573-7. doi: 10.1152/ajpendo.1989.257.4.E573.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blotting, Northern
  • Creatine Kinase / genetics
  • Creatine Kinase / metabolism*
  • DNA / genetics
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / enzymology*
  • Insulin / therapeutic use
  • Isoenzymes
  • Male
  • Myocardium / enzymology*
  • RNA, Messenger / metabolism*
  • Rats
  • Rats, Inbred Strains
  • Reference Values

Substances

  • Insulin
  • Isoenzymes
  • RNA, Messenger
  • DNA
  • Creatine Kinase