Aim: 

Type II diabetes is frequently associated with declining cardiac performance. The aim of our study was to reveal the Ca²⁺_i-handling disorders potentially underlying the contractile dysfunction characterizing diabetic cardiomyopathy.

Methods: 

In our study we used 6 months old hyperglycaemic "db/db" mice expressing leptin-resistant leptin receptors. Age-matched C57/BL6 mice were used as controls. Left ventricular wall dimensions and in vivo performance of the heart were assessed by echocardiography under pentobarbiturate anaesthesia. [Ca²⁺_i] changes and haemodynamic performance were investigated in isolated perfused hearts. For assessment of SERCA2a function cyclopiazonic acid (CPA), an inhibitor of the pump was infused.

Results: 

In 6 months old "db/db" mice blood glucose level increased and obesity was observed. Left ventricular septal thickness was increased in diabetic hearts (IVSd: Control: 0.12 ± 0.01; "db/db": 0.14 ± 0.01 mm). +dP/dt_max (Control: 3611 ± 384; "db/db": 2701 ± 428 mmHg/s), and –dP/dt_max (Control: 2535 ± 33; "db/db": 1722 ± 390 mmHg/s) of isolated "db/db" hearts were reduced compared to control hearts. Analysis of the recorded Ca²⁺_i-transients showed elevated end-diastolic Ca²⁺_i-level (Control: 172 ± 89; "db/db": 409 ± 70 nM), reduced Ca²⁺_i-transient amplitude (Control: 364 ± 97; "db/db": 218 ± 67 nM), and diminished rate of Ca²⁺ -release (RyR2 function) (+dCa/dt_max: Control: 15483 ± 3858; "db/db": 9294 ± 2027nM/s) and Ca²⁺ -sequestration (SERCA2a function) (-dCa/dt_max: Control: 9434 ± 2641; "db/db": 6217 ± 1817 nM/s) in the hearts of "db/db" mice.

Conclusion: 

The observed defects of Ca²⁺ -releasing and -sequestering processes in the hearts of type II diabetic mice suggest expressional disorders and/or altered posttranslational modification of RyR2 and SERCA2a transporters.