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-[C-11] glucose (3-[C-11]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-[C-11] OMG activity in regions of interest placed on oxidative ( soleus) compared with glycolytic ( tibialis anterior) muscle. Insulin dose- responsive increases of 3-[C-11] 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-[C-11] 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(3), 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 k(3) were similar in soleus and tibialis anterior, suggesting similar kinetics for transport, but compartmental modeling indicated a higher value in soleus for k(1), denoting higher rates of 3-[C-11] 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.