Echocardiographic assessment of cardiac function in diabetic db/db and transgenic db/db-hGLUT4 mice.
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.
Department of Pharmacology and Therapeutics, University of Calgary, Calgary, Alberta, Canada T2N 4N1.
Lisa M
LM
Semeniuk
Albert J
AJ
Kryski
David L
DL
Severson
D000818:Animals; D009202:Cardiomyopathies / Q000000981:diagnostic imaging* / Q000209:etiology; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000000981:diagnostic imaging*; D003971:Diastole / Q000502:physiology*; D004452:Echocardiography / Q000592:standards / Q000706:statistics & numerical data; D051275:Glucose Transporter Type 4; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009004:Monosaccharide Transport Proteins / Q000235:genetics*; D009124:Muscle Proteins; D015588:Observer Variation; D015203:Reproducibility of Results; D013599:Systole / Q000502:physiology*
D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495693:Slc2a4 protein, mouse