Decrease in calcium-sensing receptor in the progress of diabetic cardiomyopathy

To observe the dynamic expression of calcium-sensing receptor (CaSR) in myocardium of diabetic rats and explore its role in diabetic cardiomyopathy (DCM), 40 male Wistar rats were randomly divided into 4 groups including control, diabetic-4 weeks, diabetic-8 weeks and spermine treatment groups (240 mu M of spermine in drinking water). The type 2 Diabetes mellitus (DM) models were established by intraperitoneal injection of streptozotocin (STZ, 30 mg/kg) after high-fat and high-sugar diet for one month. The echocardiographic parameters were measured, cardiac morphology was observed by electron microscope and HE staining. The intracellular calcium concentration ([Ca2+](i)) was detected by laser-scanning confocal microscope. Western blot analyzed the expression of CaSR, protein kinase C alpha(PKC-alpha) and calcium handling regulators, such as phospholamban (PLN), Ca2+-ATPase (SERCA), and ryanodine receptor (RyR). Compared with control group, [Ca2+](i) and the expression of CaSR, RyR and SERCA/PLN were decreased, while PKC-alpha and PLN were significantly increased in a time-dependent manner in diabetic groups. Meanwhile diabetic rats displayed abnormal cardiac structure and systolic and diastolic dysfunction, and spermine (CaSR agonist) could prevent or slow its progression. These results indicate that the CaSR expression of myocardium is reduced in the progress of DCM, and its potential mechanism is related to the impaired intracellular calcium homeostasis. (C) 2011 Elsevier Ireland Ltd. All rights reserved.