Dose-responsive insulin regulation of glucose transport in human skeletal muscle
Dose-responsive insulin regulation of glucose transport in human skeletal muscle
复制标题
DOI：
10.1152/ajpendo.00598.2004
复制
发表时间：
2006-06-01
影响因子：
5.1
通讯作者：
Kelley, DE
中科院分区：
文献类型：
--
作者：
Pencek, RR;Bertoldo, A;Kelley, DE
葡萄糖转运被认为是控制胰岛素刺激的骨骼肌利用葡萄糖的主要速率控制步骤。为了评估人体骨骼肌的这一步骤，在健康志愿者进行两步胰岛素输注期间，使用3- o-甲基-[C-11]葡萄糖（3-[C-11]OMG）对骨骼肌进行定量PET成像[n = 8；30和120亩。分钟(1)。m(-2)，低（LO）和高（HI）]和基础条件（n = 8）。正电子发射断层扫描图像与MRI共同注册，以评估3-[C-11] OMG在氧化肌（比目鱼肌）和糖溶肌（胫前肌）感兴趣区域的活性。3-[C-11] OMG活性随胰岛素剂量的增加而升高（P < 0.01）。比目鱼肌组织活性明显高于胫骨前肌（P < 0.05）。光谱分析确定了两个数学成分相互作用，形成组织活性曲线。这两种成分在生理学上被解释为可能代表3-[C-11] OMG从血浆输送到组织的动力学和双向葡萄糖运输的动力学。在低血糖期间，与基线相比，k(3)增加了6倍，这是归因于向内葡萄糖运输的速率常数，在高血糖期间又增加了3倍（0.012 +/- 0.003,0.070 +/- 0.014,0.272 +/- 0.059 min(-1), P < 0.001）。k(3)在比目鱼肌和胫骨前肌中的值相似，表明运输动力学相似，但室室模型显示比目鱼肌中k(1)的值更高，表明3-[C-11] OMG输送到比目鱼肌的比率高于胫骨前肌。总之，在健康志愿者中，胰岛素对骨骼肌中葡萄糖转运有强大的剂量反应性刺激。
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.