Minimal Amount of Insulin Can Reverse Diabetic Heart Function Sarcoplasmic Reticulum Ca<SUP>2&#8290;</SUP> Transport and Phospholamban Protein Expression

Minimal Amount of Insulin Can Reverse Diabetic Heart Function Sarcoplasmic Reticulum Ca<SUP>2&#8290;</SUP> Transport and Phospholamban Protein Expression

<P> In the present study, the underlying mechanisms for diabetic functional derangement and insulin effect on diabetic cardiomyopathy were investigated with respect to sarcoplasmic reticulum (SR) Ca<SUP>2&#8290;</SUP>-ATPase and phospholamban at the transcriptional and translational levels. The maximal Ca<SUP>2&#8290;</SUP> uptake and the affinity of Ca<SUP>2&#8290;</SUP>-ATPase for Ca<SUP>2&#8290;</SUP> were decreased in streptozotocin-induced diabetic rat cardiac SR, however, even minimal amount of insulin could reverse both parameters. Levels of both mRNA and protein of phospholamban were significantly increased in diabetic rat hearts, whereas the mRNA and protein levels of SR Ca<SUP>2&#8290;</SUP>-ATPase were significantly decreased. In case of phospholamban, insulin treatment reverses these parameters to normal levels. Minimal amount of insulin could reverse the protein levels; however, it could not reverse the mRNA level of SR Ca<SUP>2&#8290;</SUP>-ATPase at all. Thus, the decreased SR Ca<SUP>2&#8290;</SUP> uptake appear to be largely attributed to the decreased SR Ca<SUP>2&#8290;</SUP>-ATPase level, which is further impaired due to the inhibition by the increased level of phospholamban. These results indicate that insulin is involved in the control of intracellular Ca<SUP>2&#8290;</SUP> in the cardiomyocyte through multiple target proteins via multiple mechanisms for the decrease in the mRNA for both SR Ca<SUP>2&#8290;</SUP>-ATPase and phospholamban which are unknown and needs further study.