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and Phosphorylated Phospholamban in Diabetic Rat Hearts
1 Department of Pharmacology and Cell Biophysics, University of Cincinnati, Cincinnati, OH, USA
2 Department of Oral Biology, Ohio State University, Columbus, OH, USA
* To whom correspondence should be addressed. E-mail: matlibma{at}email.uc.edu.
The objective of the study was to determine whether a gender difference exists either in myosin heavy chain (MHC) isoform or in sarcoplasmic reticulum (SR) protein levels in diabetic rat hearts. As is the case of normal rodent hearts, all four chambers of the control rat hearts had almost 100% MHC-
. MHC-
expression in ventricles of male 6-week diabetic rats was significantly greater (78 ± 7 %) compared to that of female 6-week diabetic rats (50 ± 5 %). The cardiac SR Ca2+-ATPase (SERCA2a) protein level was decreased and the phospholamban (PLB) protein level was increased in the left ventricle of diabetic rats, but there was no difference between male and female diabetic rats. The phosphorylated PLB level was decreased more in male diabetic rats than in female diabetic rats. Insulin treatment completely normalized blood glucose level and cardiac SERCA2a and PLB protein levels, and the decrease in MHC-
level in both male and female diabetic rats. Insulin treatment completely normalized serum insulin and almost completely normalized phosphorylation of PLB at serine-16 in male diabetic rats. Insulin treatment completely normalized serum insulin level in male diabetic rats, but only partially normalized in female diabetic rats. Although insulin treatment almost completely normalized phosphorylation of PLB at threonine-17 in female diabetic rats, the increase was significantly more than insulin-treated male diabetic rats. It is concluded that higher levels of MHC-b and dephosphorylated PLB may contribute to more contractile dysfunction in the male diabetic rat hearts than female diabetic rat hearts and that phosphorylation of PLB at threonine-17 more responsive to insulin treatment in female diabetic rat hearts.
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