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Insulin responsiveness of CK-M and CK-B mRNA in the diabetic rat heart
B K Popovich1, M R Sayen, W H Dillmann
1Department of Medicine, University of California, San Diego 92103.
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)
Insights
Diabetes mellitus significantly reduces heart creatine kinase (CK) gene expression, impacting cardiac function. Insulin therapy can restore these critical gene levels, offering potential therapeutic insights for diabetic heart disease.
Area of Science:
- Molecular biology
- Cardiovascular research
- Endocrinology
Background:
- Diabetes mellitus is linked to decreased cardiac performance.
- Molecular mechanisms underlying diabetic cardiomyopathy are not fully understood.
- Insulin-responsive cardiac gene products with known functions are poorly described.
Purpose of the Study:
- To investigate the impact of experimental diabetes on creatine kinase (CK) gene expression in the rat heart.
- To determine if diabetes affects both CK-M and CK-B mRNA levels.
- To assess the effect of insulin administration on these mRNA levels.
Main Methods:
- Quantification of CK-M and CK-B mRNA levels using Northern blot analysis with specific cDNA probes in rat hearts.
- Induction of experimental diabetes mellitus in rats.
- Administration of acute and chronic insulin therapy to diabetic rats.
Main Results:
- Diabetic rat hearts showed significantly reduced CK-B mRNA (19.8% of control) and CK-M mRNA (46.5% of control) levels.
- Acute insulin injection increased CK-M and CK-B mRNA levels within 5 hours.
- Chronic insulin therapy normalized CK-M mRNA and substantially increased CK-B mRNA levels, exceeding normal values.
Conclusions:
- Diabetes mellitus markedly lowers both CK-M and CK-B mRNA levels in the rat heart.
- Insulin plays a crucial role in regulating cardiac CK gene expression.
- These findings highlight potential molecular targets for managing diabetic cardiomyopathy.