Slowed relaxation in diabetic cardiomyopathy (CM) is partially related to 
diminished expression of the sarcoplasmic reticulum (SR) Ca2+-ATPase SERCA2a. To 
evaluate the impact of SERCA2a overexpression on SR Ca2+ handling in diabetic 
CM, we 1) generated transgenic rats harboring a human cytomegalovirus 
enhancer/chicken beta-actin promotor-controlled rat SERCA2 transgene 
(SERCA2-TGR), 2) characterized their SR phenotype, and 3) examined whether 
transgene expression may rescue SR Ca2+ transport in streptozotocin-induced 
diabetes. The transgene was expressed in all heart chambers. Compared to 
wild-type (WT) rats, a heterozygous line exhibited increased SERCA2 mRNA 
(1.5-fold), SERCA2 protein (+26%) and SR Ca2+ uptake (+37%). Phospholamban 
expression was not altered. In SERCA2-TGR, contraction amplitude (+48%) and 
rates of contraction (+34%) and relaxation (+35%) of isolated papillary muscles 
(PM) were increased (P2+ uptake and SERCA2 protein of SERCA2-TGR were 1.3-fold 
higher (P2+ uptake, accelerates relaxation and compensates, in part, for 
depressed Ca2+ uptake in diabetic CM. Therefore, SERCA2 expression might 
constitute an important therapeutic target to rescue cardiac SR Ca2+ handling in 
diabetes.