Basal and Exercise-Stimulated Cardiac Glucose Uptake Is Preserved in GLUT4 Null Mice
Abstract Number: 996-P
Authors: PATRICK T. FUEGER, JULIO E. AYALA, JANE SHEARER, DEANNA P. BRACY, MAUREEN J. CHARRON, JEFFREY N. ROTTMAN, DAVID H. WASSERMAN.
Institutions: Durham, NC; Nashville, TN; Bronx, NY.
Results: A complete loss of GLUT4 severely impairs basal and exercise-stimulated glucose uptake in skeletal muscle. The aim of this study was to determine if cardiac glucose uptake was altered in GLUT4 null mice in vivo. Thus, C57BL/6J mice with a total GLUT4 knockout (G4KO) were compared to their wild type littermates (WT) at 4 mo of age. Mice were subjected to echocardiography, tail cuff plethysmography, and a protocol designed to measure glucose uptake (Rg) using 2-deoxy[3H]glucose in vivo during rest or treadmill exercise. Compared to WT, G4KO had increased left ventricular mass (92±8 vs. 121±10 mg, p<0.01), absolute (116±5 vs. 150±7 mg, p<0.01) and relative (4.4±0.1 vs. 6.7±0.3, p<0.01) cardiac mass, and cardiac glycogen (0.6±0.1 vs. 1.3±0.2 mg/g, p<0.01). Fractional shortening was decreased in G4KO compared to WT (46±3 vs. 54±1 %, p<0.01). Resting heart rate and systolic blood pressure were not different between WT and G4KO. Basal cardiac Rg was not different between WT and G4KO (23.3±6.3 vs. 25.5±7.9 μmol/100g/min). Exercise increased cardiac Rg and again there were no significant differences between WT and G4KO (39.8±8.3 vs. 52.4±12.9 μmol/100g/min). By comparison G4KO had severely limited Rg relative to WT in gastrocnemius (basal: 2.6±0.5 vs. 1.4±0.4 μmol/100g/min, p<0.05; exercise: 24.4±4.7 vs. 1.9±0.3 μmol/100g/min, p<0.01) and soleus (basal: 32.4±5.7 vs. 13.8±3.7 μmol/100g/min, p<0.05; exercise: 53.7±6.4 vs. 20.6±2.8 μmol/100g/min, p<0.01) muscles. In summary, unlike skeletal muscle, cardiac muscle is not prone to aberrant glucose metabolism when GLUT4 is chronically reduced. However, GLUT4 null hearts are hypertrophic and exhibit impaired function. Therefore, while GLUT4 is not necessary in the acute regulation of cardiac glucose metabolism it is essential for normal cardiac structure and function.