IGF1- and insulin receptors modulate a variety of functions in cardiac myocytes, including cell growth, metabolism and apoptosis. We could show that inducible inactivation of the myocardial IGF1-R in adult mice resulted only in aged mice in development of diastolic dysfunction. Here we addressed the question to what extent Insulin dependent signalling could compensate for the loss of IGF-1 signalling in cardiac myocytes in young animals. Therefore, we inactivated IGF1-R expression by injection of 4-OH-Tamoxifen. Four weeks later Streptozotocin (STZ) (40 mg/kg, 5 x) was injected to eliminate Insulin producing b-cells. STZ treatment elevated blood glucose levels and induced glucose intolerance. Depending on the blood glucose levels a low (mean 230 mg/dl) and a high (mean 390 mg/dl) blood glucose group were defined. Cardiac function was assessed in vivo by MRI and P-V catheter measurements. MRI analysis revealed no alterations of end systolic and end diastolic volumes, heart rate or ejection fraction. Micro tip catheter measurements of cardiac pressure-volume changes demonstrated that diabetes resulted in an enhanced end-diastolic pressure (1.6 mmHg basal vs 4.2 mmHg STZ) in the high blood glucose group. Moreover, relaxation time constant t was significantly enhanced indicating the development of diastolic dysfunction. However, these alterations were similar in WT and IGF1-R KO mice.

Conclusion: 

Loss of insulin signalling results in the development of cardiac diastolic dysfunction. This effect is not altered by IGF1-R signalling in cardiac myocytes.

Cardiac Electrophysiology