AIM: To study whether calcium-modulating proteins CASQ2, FKBP12.6 and SERCA2a 
participate in diabetic cardiomyopathy, and whether the beneficial actions of 
testosterone, sildenafil or fructose diphosphate Sr (FDP-Sr) in the treatment of 
diabetic cardiomyopathy result from suppressing these molecules.
METHODS: Fifty male Sprague-Dawley (SD) rats were divided into five groups. 
Except for the normal group (non-diabetic), the other four groups were injected 
with streptozotocin (STZ, 60 mg/kg, ip) to induce diabetes. Four weeks after STZ 
injection, the four groups received sildenafil (12 mg·kg(-1)·d(-1), ig, for 4 
week), FDP-Sr (200 mg/kg, ig, for 4 week), testosterone propionate (4 
mg·kg(-1)·d(-1), sc, for 4 week), or no treatment, respectively.
RESULTS: In the diabetic rats, blood glucose, free fatty acids, triglycerides, 
total cholesterol, and low-density lipoprotein cholesterol (LDL-C) were 
significantly increased, while high-density lipoprotein cholesterol (HDL-C) was 
significantly reduced, as compared to the non-diabetic rats. Cardiac dysfunction 
and myocardial hypertrophy of the diabetic rats were associated with increased 
mRNA and protein expression of iNOS, OBRb, and PKCɛ, while expression of CASQ2, 
SERCA2a, and FKBP12.6 was significantly down-regulated. Sildenafil and FDP-Sr, 
but not testosterone, significantly attenuated the biomarker abnormalities, 
without changing the metabolic abnormalities.
CONCLUSION: CASQ2, FKBP12.6 and SERCA2a were down-regulated in diabetic 
cardiomyopathy. Sildenafil and FDP-Sr, but not testosterone, attenuated the 
cardiac dysfunction in diabetic cardiomyopathy, without changing the metabolic 
abnormalities, which may results from inhibiting oxidative and inflammatory 
cytokines and improving calcium homeostasis.