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Altered SR protein expression associated with contractile dysfunction in diabetic rat hearts
1Department of Pharmacology and Cell Biophysics, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0575, USA.
American Journal of Physiology. Heart and Circulatory Physiology
|August 22, 2001
Summary
Diabetic rat hearts show impaired relaxation and contraction due to changes in sarcoplasmic reticulum proteins. Insulin therapy restored normal protein levels and heart function, highlighting a key mechanism in diabetic cardiomyopathy.
Area of Science:
- Cardiology
- Molecular Biology
- Endocrinology
Background:
- Diabetic cardiomyopathy is a significant complication of diabetes mellitus.
- Alterations in cardiac sarcoplasmic reticulum (SR) protein function contribute to heart dysfunction.
Purpose of the Study:
- To investigate the association between SR protein level alterations and diastolic/systolic dysfunction in streptozotocin-induced diabetic rat hearts.
- To determine the effects of insulin treatment on SR protein expression and cardiac function in diabetic rats.
Main Methods:
- Induction of diabetes in rats using streptozotocin.
- Assessment of cardiac function (relaxation and contraction) at 4 and 6 weeks post-induction.
- Quantification of sarcoplasmic reticulum protein levels (phospholamban, SERCA2) and their phosphorylation status.
- Evaluation of SR Ca2+ uptake kinetics (affinity and maximum rate).
- Administration of insulin to diabetic rats and subsequent assessment of SR protein expression and function.
Main Results:
- Four-week diabetic rat hearts showed impaired relaxation, while 6-week diabetic hearts exhibited both impaired relaxation and contraction.
- Increased total phospholamban and decreased phosphorylated phospholamban levels were observed in diabetic hearts.
- Sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2) protein levels decreased in 6-week diabetic hearts.
- SR Ca2+ uptake affinity was reduced in 4-week diabetic hearts, with further reductions in affinity and maximum rate in 6-week diabetic hearts.
- Insulin treatment normalized SR protein expression and cardiac function.
Conclusions:
- Early diastolic dysfunction in diabetic rats is linked to increased non-phosphorylated phospholamban and reduced SR Ca2+ pump affinity.
- Late systolic dysfunction is associated with decreased SERCA2 levels, reduced SR Ca2+ pump affinity, and maximum velocity.
- Insulin therapy effectively reverses these molecular and functional deficits in the diabetic heart.