AJP - Heart Calcium Transients and Cell-Sarcomere
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Am J Physiol Heart Circ Physiol 285: H2688-H2693, 2003. First published August 21, 2003; doi:10.1152/ajpheart.00547.2003
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Gender differences in myosin heavy chain-{beta} and phosphorylated phospholamban in diabetic rat hearts

Yan Zhong,1 Peter J Reiser,2 and Mohammed A. Matlib1

1Department of Pharmacology and Cell Biophysics, College of Medicine, University of Cincinnati, Cincinnati 45267-0575; and 2Department of Oral Biology, Ohio State University, Columbus, Ohio 43210-1267

Submitted 12 June 2003 ; accepted in final form 23 July 2003

The objective of this study was to determine whether a gender difference exists in myosin heavy chain (MHC) isoform or sarcoplasmic reticulum protein levels in diabetic rat hearts. As is the case with normal rodent hearts, all four chambers of the control rat hearts expressed almost 100% MHC-{alpha}. In 6-wk diabetic rats, MHC-{beta} expression in ventricles of males was significantly greater (78 ± 7%) than in females (50 ± 5%). The cardiac sarco(endo)plasmic reticulum 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 than in female diabetic rats. Insulin treatment completely normalized blood glucose level, cardiac SERCA2a and PLB protein levels, and the decrease in MHC-{beta} levels 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. Although insulin treatment completely normalized serum insulin levels in male diabetic rats, in females it only partially normalized serum insulin levels. Also, insulin treatment almost completely normalized phosphorylation of PLB at threonine 17 in female diabetic rats; however, the increase was significantly greater than that identified for insulin-treated male diabetic rats. We conclude that higher levels of MHC-{beta} and dephosphorylated PLB may contribute to more contractile dysfunction in male than in female diabetic rat hearts, and that phosphorylation of PLB at threonine 17 is more responsive to insulin in female diabetic rat hearts.

diabetes; cardiomyopathy; sarcoplasmic reticulum; calcium ATPase


Address for reprint requests and other correspondence: M. A. Matlib, Dept. of Pharmacology and Cell Biophysics, Univ. of Cincinnati College of Medicine, 231 Albert B. Sabin Way, PO Box 670575, Cincinnati, OH 43267-0575 (E-mail: matlibma{at}email.uc.edu).






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