Echocardiographic assessment of cardiac function in diabetic db/db and transgenic db/db-hGLUT4 mice

1 Department of Pharmacology and Therapeutics and 2 Department of Medicine, University of Calgary, Calgary, Alberta, Canada T2N 4N1 Control db /+ and diabetic db / db mice at 6 and 12 wk of age were subjected to echocardiography to determine whether contractile function was reduced in vivo and restored in transgenic db / db -human glucose transporter 4 (hGLUT4) mice (12 wk old) in which cardiac metabolism has been normalized. Systolic function was unchanged in 6-wk-old db / db mice, but fractional shortening and velocity of circumferential fiber shortening were reduced in 12-wk-old db / db mice (43.8 ± 2.1% and 8.3 ± 0.5 circs/s, respectively) relative to db /+ control mice (59.5 ± 2.3% and 11.8 ± 0.4 circs/s, respectively). Doppler flow measurements were unchanged in 6-wk-old db / db mice. The ratio of E and A transmitral flows was reduced from 3.56 ± 0.29 in db /+ mice to 2.40 ± 0.20 in 12-wk-old db / db mice, indicating diastolic dysfunction. Thus a diabetic cardiomyopathy with systolic and diastolic dysfunction was evident in 12-wk-old diabetic db / db mice. Cardiac function was normalized in transgenic db / db -hGLUT4 mice, indicating that altered cardiac metabolism can produce contractile dysfunction in diabetic db / db hearts. echocardiography; human glucose transporter 4