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1 Medicine, University of Pittsburgh, Pittsburgh, PA, USA
2 Information Engineering, University of Padova, Padova, Italy
3 Radiology, University of Pittsburgh, Pittsburgh, PA, USA
* To whom correspondence should be addressed. E-mail: pencekr{at}msx.dept-med.pitt.edu.
Glucose transport is regarded as the principal rate control step governing insulin-stimulated glucose utilization by skeletal muscle. To assess this step in human skeletal muscle, quantitative PET imaging of skeletal muscle was performed using [11C]3-OMG in healthy volunteers during a two-step insulin infusion (n=8; 30 and 120 mU/min-m2, LO and HI) and during basal conditions (n=8). PET images were co-registered with MRI to assess [11C]3-OMG activity in regions of interest placed on oxidative (soleus) compared to glycolytic (tibialis anterior) muscle. Insulin dose-responsive increases of [11C]3-OMG activity in muscle were observed (p<0.01). Tissue activity was greater in soleus than in tibialis anterior (p<0.05). Spectral analysis identified that two mathematical components interacted to shape tissue activity curves. These two components were interpreted physiologically as likely representing the kinetics of [11C]3-OMG delivery from plasma to tissue, and the kinetics of bi-directional glucose transport. During LO as compared to BASAL, there was a 6-fold increase in k3, the rate constant attributed to inward glucose transport, and another 3-fold increase during HI (0.012±0.003 min-1, 0.070±0.014 min-1, 0.272±0.059 min-1; p<0.001). Values for k3 were similar in soleus and tibialis anterior, suggesting similar kinetics for transport, but compartmental modeling indicated a higher value in soleus for k1, denoting higher rates of [11C]3-OMG delivery to soleus than to tibialis anterior. In summary, in healthy volunteers there is robust dose-responsive insulin stimulation of glucose transport in skeletal muscle.
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