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First published online May 14, 2009, 10.2967/jnumed.109.062687
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Uptake of 18F-Labeled 6-Fluoro-6-Deoxy-D-Glucose by Skeletal Muscle Is Responsive to Insulin Stimulation

Chandra Spring-Robinson1, Visvanathan Chandramouli2, William C. Schumann2, Peter F. Faulhaber3, Yanming Wang3,4, Chunying Wu3,4, Faramarz Ismail-Beigi2 and Raymond F. Muzic, Jr.1,3,4

1 Department of Biomedical Engineering, University Hospitals Case Medical Center, School of Medicine, Case Western Reserve University, Cleveland, Ohio; 2 Department of Medicine, University Hospitals Case Medical Center, School of Medicine, Case Western Reserve University, Cleveland, Ohio; 3 Department of Radiology, University Hospitals Case Medical Center, School of Medicine, Case Western Reserve University, Cleveland, Ohio; and 4 Case Center for Imaging Research, University Hospitals Case Medical Center, School of Medicine, Case Western Reserve University, Cleveland, Ohio


Figure 1
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FIGURE 1.  (Top) Glucose infusion rate over duration of typical experiment. Insulin infusion was begun at 35 min, and glucose infusion rate was increased to maintain plasma glucose concentration at approximately 6 mM. (Middle) Observed glucose concentrations. Data showed that glucose concentrations were similar under basal and insulin-stimulated conditions. (Bottom) Times of injection of 18F-6FDG (arrows) and resultant time courses of activity in gastrocnemius muscle (solid curves) under basal and insulin-stimulated conditions. Contribution of activity from that remaining from first scan was removed from second scan by extrapolation (dashed curve) and subtraction.

 

Figure 2
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FIGURE 2.  CT images (gray scale) fused with PET images (color scale) of same rat in basal state (top) and high-insulin state (middle and bottom), illustrating data analysis procedure and typical imaging results. Contours illustrate boundaries of VOIs. Rat was lying prone with its hind legs extended caudally. These images reflected tissue activity between 0 and 30 min after 18F-6FDG injection. FIB = fibula; GASTROC = gastrocnemius; TIB = tibia; TIB ANT = tibialis anterior.

 

Figure 3
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FIGURE 3.  Plasma glucose concentrations measured in arterial blood samples collected every 5 min. With perfect glucose clamp, concentrations should be same in all states. Concentration of 5.3 ± 0.3 mM measured during low-insulin state was slightly lower than concentration of 6.2 ± 0.4 mM measured during basal state in these animals, although this small difference was statistically significant. Concentrations in high-insulin state and basal state were both 5.9 ± 0.5 mM. Error bars denote SE for basal state (n = 9) and high-insulin state (n = 7) and were omitted for low-insulin state (n = 2).

 

Figure 4
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FIGURE 4.  Average GIR needed to maintain 6 mM plasma glucose concentration. This value was higher during low-insulin (n = 2) and high-insulin (n = 7) infusions than at baseline (n = 9). Error bars denote SE.

 

Figure 5
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FIGURE 5.  Tissue time–activity curves for gastrocnemius muscle during scans acquired under high-insulin conditions (n = 7), low-insulin conditions (n = 2), and basal conditions (n = 9), demonstrating increased 18F-6FDG uptake caused by insulin administration. Error bars are not shown for low insulin because of small number of subjects, although maximum difference between individual curves from 2 rats was 25%.

 

Figure 6
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FIGURE 6.  Bone marrow time–activity curves in basal, low-insulin, and high-insulin states. These curves were comparable, indicating lack of effect of insulin stimulation on glucose transport in marrow. This result was in contrast to effect observed in skeletal muscle in Figure 5.

 





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