Insulin responsiveness of CK-M and CK-B mRNA in the diabetic rat heart

Abstract

Decreased cardiac performance is a known complication of diabetes mellitus, but the detailed molecular mechanisms that are responsible for this contractile abnormality are only incompletely explored, and cardiac gene products of known function, which are markedly and actively insulin responsive, have not been described. Recently, we found that creatine kinase (CK) enzyme activity and CK-M subunit mRNA levels are decreased in the heart of rats with experimental diabetes mellitus. These abnormalities could be restored to normal with chronic insulin administration. The CK-M and CK-B genes are expressed in the heart, and we wanted to determine whether diabetes also induces a change in CK-B mRNA levels. Quantitation of CK-M and CK-B mRNA levels on Northern blots with specific cDNA probes showed that, in diabetic hearts, CK-B mRNA levels represent only 19.8% of control levels and are more markedly depressed than CK-M mRNA levels, which are 46.5% of control values. Acute injection of insulin led to a significant 1.6-fold increase in CK-M mRNA and a 2.2-fold increase of CK-B mRNA 5 h after insulin injection. CK-M mRNA levels were restored to normal within 12 h, but 48 h were required to restore CK-B mRNA levels to normal values. After 1 mo of insulin therapy, CK-B mRNA levels had risen 9.7-fold, exceeding normal values by 90%, whereas CK-M mRNA levels were at the normal level as previously shown. CK enzyme activity showed only a small response to insulin administration 48 h postinjection. Diabetes leads therefore to a marked lowering of CK-M and CK-B mRNA levels in the rat heart.(ABSTRACT TRUNCATED AT 250 WORDS)

Temporal response pattern of biochemical analytes in experimental diabetes

“…Insulin and the thyroid hormones have been considered to be powerful regulators of the enzyme CK. Low insulin provokes destabilization of its mRNA [31], while insulin treatment has led to recuperation of the loss of CK isoenzyme MB and CK isoenzyme BB activity in diabetic rats [32]. Although we used the same animal model and similar duration of experiment and severity of diabetes in our study of CK activity, we found no significant change in its serum level (Figure 3).…”

Incidence, Predictors, and Significance of Abnormal Cardiac Enzyme Rise in Patients Treated With Bypass Surgery in the Arterial Revascularization Therapies Study (ARTS)

“…21 These findings may be explained by a decline in creatine kinase activity related to diabetes as demonstrated in animal studies. 22,23 Finally, intensified medical management in the treatment of these high-risk patients, either in the time interval between screening and surgery or during the procedure, cannot be completely ruled out as an explanation for our findings.…”