Diabetic cardiomyopathy (DCM) is a diabetic complication, which results in 
myocardial dysfunction independent of other etiological factors. Abnormal 
intracellular calcium ([Ca(2+)](i)) homeostasis has been implicated in DCM and 
may precede clinical manifestation. Studies in cardiomyocytes have shown that 
diabetes results in impaired [Ca(2+)](i) homeostasis due to altered sarcoplasmic 
reticulum Ca(2+) ATPase (SERCA) and sodium-calcium exchanger (NCX) activity. 
Importantly, altered calcium homeostasis may also be involved in 
diabetes-associated endothelial dysfunction, including impaired 
endothelium-dependent relaxation and a diminished capacity to generate nitric 
oxide (NO), elevated cell adhesion molecules, and decreased angiogenic growth 
factors. However, the effect of diabetes on Ca(2+) regulatory mechanisms in 
cardiac endothelial cells (CECs) remains unknown. The objective of this study 
was to determine the effect of diabetes on [Ca(2+)](i) homeostasis in CECs in 
the rat model (streptozotocin-induced) of DCM. DCM-associated cardiac fibrosis 
was confirmed using picrosirius red staining of the myocardium. CECs isolated 
from the myocardium of diabetic and wild-type rats were loaded with Fura-2, and 
UTP-evoked [Ca(2+)](i) transients were compared under various combinations of 
SERCA, sarcoplasmic reticulum Ca(2+) ATPase (PMCA) and NCX inhibitors. Diabetes 
resulted in significant alterations in SERCA and NCX activities in CECs during 
[Ca(2+)](i) sequestration and efflux, respectively, while no difference in PMCA 
activity between diabetic and wild-type cells was observed. These results 
improve our understanding of how diabetes affects calcium regulation in CECs, 
and may contribute to the development of new therapies for DCM treatment.