Korean J Physiol Pharmacol.
1999 Apr;3(2):175-182.
Minimal amount of insulin can reverse diabetic heart function: Sarcoplasmic reticulum Ca2+ transport and phospholamban protein expression
- Affiliations
-
- 1Department of Pharmacology, University of Ulsan College of Medicine, 388-1 Poongnapdong, Songpa- South Korea.
Abstract
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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) Ca2+-ATPase
and phospholamban at the transcriptional and translational levels. The
maximal Ca2+ uptake and the affinity of Ca2+-ATPase for Ca2+ 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
Ca2+-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 Ca2+-ATPase at all. Thus, the
decreased SR Ca2+ uptake appear to be largely attributed to the
decreased SR Ca2+-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 Ca2+
in the cardiomyocyte through multiple target proteins via multiple
mechanisms for the decrease in the mRNA for both SR Ca2+-ATPase and
phospholamban which are unknown and needs further study.