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

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-[[sup.11]C]glucose (3-[[sup.11]C]OMG) in healthy volunteers during a two-step insulin infusion [n = 8; 30 and 120 mU*[min.sup.-1*m.sup.-2], low (LO) and high (HI)] and during basal conditions (n = 8). Positron emission tomography images were coregistered with MRI to assess 3-[[sup.11]C]OMG activity in regions of interest placed on oxidative (soleus) compared with glycolytic (tibialis anterior) muscle. Insulin dose-responsive increases of 3-[[sup.11]C]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-[[sup.11]C]OMG delivery from plasma to tissue and the kinetics of bidirectional glucose transport. During low compared with basal, there was a sixfold increase in [k.sub.3], the rate constant attributed to inward glucose transport, and another threefold increase during HI (0.012 [+ or -] 0.003, 0.070 [+ or -] 0.014, 0.272 [+ or -] 0.059 [min.sup.-1], P < 0.001). Values for [k.sub.3] were similar in soleus and tibialis anterior, suggesting similar kinetics for transport, but compartmental modeling indicated a higher value in soleus for [k.sub.1], denoting higher rates of 3-[[sup.11]C]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