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Dose-responsive insulin regulation of glucose transport in human skeletal muscle

Departments of ¹Medicine and ²Radiology, University of Pittsburgh, Pittsburgh, Pennsylvania; and ³Department of Information Engineering, University of Padova, Padua, Italy

Submitted 20 December 2004 ; accepted in final form 21 December 2005

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 3-O-methyl-[¹¹C]glucose (3-[¹¹C]OMG) in healthy volunteers during a two-step insulin infusion [n = 8; 30 and 120 mU·min^–1·m^–2, low (LO) and high (HI)] and during basal conditions (n = 8). Positron emission tomography images were coregistered with MRI to assess 3-[¹¹C]OMG activity in regions of interest placed on oxidative (soleus) compared with glycolytic (tibialis anterior) muscle. Insulin dose-responsive increases of 3-[¹¹C]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 3-[¹¹C]OMG delivery from plasma to tissue and the kinetics of bidirectional glucose transport. During low compared with basal, there was a sixfold increase in k₃, the rate constant attributed to inward glucose transport, and another threefold increase during HI (0.012 ± 0.003, 0.070 ± 0.014, 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 3-[¹¹C]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.

glucose transport; insulin sensitivity; skeletal muscle; positron emission tomography; 3-O-methylglucose

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