Dose-responsive insulin regulation of glucose transport in human skeletal muscle
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چکیده
Pencek, R. Richard, Alessandra Bertoldo, Julie Price, Carol Kelley, Claudio Cobelli, and David E. Kelley. Dose-responsive insulin regulation of glucose transport in human skeletal muscle. Am J Physiol Endocrinol Metab 290: E1124–E1130, 2006. First published January 3, 2006; doi:10.1152/ajpendo.00598.2004.—Glucose transport is regarded as the principal rate control step governing insulinstimulated 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]glucose (3-[C]OMG) in healthy volunteers during a two-step insulin infusion [n 8; 30 and 120 mU min 1 m , low (LO) and high (HI)] and during basal conditions (n 8). Positron emission tomography images were coregistered with MRI to assess 3-[C]OMG activity in regions of interest placed on oxidative (soleus) compared with glycolytic (tibialis anterior) muscle. Insulin dose-responsive increases of 3-[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-[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 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 , 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-[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.
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