Pencek R Richard, Bertoldo Alessandra, Price Julie, Kelley Carol, Cobelli Claudio, Kelley David E
Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Am J Physiol Endocrinol Metab. 2006 Jun;290(6):E1124-30. doi: 10.1152/ajpendo.00598.2004. Epub 2006 Jan 3.
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.
葡萄糖转运被视为控制胰岛素刺激的骨骼肌葡萄糖利用的主要速率控制步骤。为了评估人类骨骼肌中的这一步骤，在健康志愿者中进行了两步胰岛素输注（n = 8；30和120 mU·min⁻¹·m⁻²，低剂量（LO）和高剂量（HI））以及基础状态（n = 8）期间，使用3-O-甲基-[¹¹C]葡萄糖（3-[¹¹C]OMG）对骨骼肌进行定量PET成像。正电子发射断层扫描图像与MRI进行配准，以评估放置在氧化（比目鱼肌）与糖酵解（胫骨前肌）肌肉上的感兴趣区域中的3-[¹¹C]OMG活性。观察到肌肉中3-[¹¹C]OMG活性随胰岛素剂量呈反应性增加（P < 0.01）。比目鱼肌中的组织活性高于胫骨前肌（P < 0.05）。频谱分析确定，两个数学成分相互作用形成组织活性曲线。这两个成分在生理上被解释为可能代表3-[¹¹C]OMG从血浆到组织的递送动力学以及双向葡萄糖转运的动力学。与基础状态相比，低剂量时，归因于内向葡萄糖转运的速率常数k3增加了六倍，高剂量时又增加了三倍（0.012 ± 0.003、0.070 ± 0.014、0.272 ± 0.059 min⁻¹，P < 0.001）。比目鱼肌和胫骨前肌中的k3值相似，表明转运动力学相似，但隔室模型表明比目鱼肌中的k1值更高，这表明3-[¹¹C]OMG递送至比目鱼肌的速率高于胫骨前肌。总之，在健康志愿者中，骨骼肌中的葡萄糖转运存在强大的剂量反应性胰岛素刺激。
