灌注速率对胰岛素介导的骨骼肌葡萄糖摄取时间进程的影响。
Effect of perfusion rate on the time course of insulin-mediated skeletal muscle glucose uptake.
作者信息
Baron A D, Brechtel-Hook G, Johnson A, Cronin J, Leaming R, Steinberg H O
机构信息
Department of Medicine, Indiana University Medical Center, Indianapolis, USA.
出版信息
Am J Physiol. 1996 Dec;271(6 Pt 1):E1067-72. doi: 10.1152/ajpendo.1996.271.6.E1067.
To better define the time course of skeletal muscle glucose uptake and its modulation by changes in perfusion, we performed systemic euglycemic-hyperinsulinemic clamps (40 mU.m-2.min-1) for a 90-min period in a group of lean, insulin-sensitive subjects (n = 9) on two occasions (approximately 4 wk apart) with insulin-mediated vasodilation intact or inhibited. Insulin-mediated vasodilation was inhibited by an intrafemoral artery infusion of NG-monomethyl-L-arginine (L-NMMA), a specific inhibitor of nitric oxide synthase. During the study, leg blood flow (LBF) and arteriovenous glucose difference (AVG delta) were measured every 10 min; leg glucose uptake (LGU) was calculated as LGU = LBF x AVG delta. The systemic insulin infusion caused a time-dependent increase in LBF from 0.194 +/- 0.024 to 0.349 +/- 0.046 l/min (P < 0.01). The intrafemoral artery infusion of L-NMMA completely inhibited this increase in LBF. AVG delta, LGU, and whole body glucose disposal rates increased in a time-dependent manner in both studies. The maximum AVG delta was lower with insulin-mediated vasodilation intact than when inhibited (25.9 +/- 2.5 vs. 35.0 +/- 1.6 mg/dl, P < 0.001). The time to achieve half-maximal (T1/2) AVG delta was somewhat longer with insulin-mediated vasodilation intact compared with inhibited (35.6 +/- 4.1 vs. 29.7 +/- 1.6 min, P < 0.01). Maximal LGU was 93.9 +/- 26.8 and 57.2 +/- 11.6 mg/min (P < 0.005), and the T1/2 LGU was 50.2 +/- 16.0 and 36.3 +/- 8.8 min (P = 0.1) during intact and inhibited insulin-mediated vasodilation, respectively. Thus insulin-mediated vasodilation has a modest effect in slowing the time course at which insulin stimulates glucose uptake but has a marked effect in augmenting the maximal rate of insulin-stimulated glucose uptake in skeletal muscle. Impaired insulin-mediated vasodilation, as observed in patients with essential hypertension, may explain, at least in part, the insulin resistance observed in these patients.
为了更好地确定骨骼肌葡萄糖摄取的时间进程及其受灌注变化的调节情况，我们对一组体型消瘦、胰岛素敏感的受试者（n = 9）进行了两次（间隔约4周）为期90分钟的全身性正常血糖 - 高胰岛素钳夹试验（40 mU·m⁻²·min⁻¹），试验中胰岛素介导的血管舒张功能保持完整或受到抑制。通过股动脉内输注一氧化氮合酶的特异性抑制剂NG - 单甲基 - L - 精氨酸（L - NMMA）来抑制胰岛素介导的血管舒张。在研究过程中，每10分钟测量一次腿部血流量（LBF）和动静脉葡萄糖差值（AVGδ）；腿部葡萄糖摄取量（LGU）通过LGU = LBF×AVGδ计算得出。全身性胰岛素输注导致LBF随时间依赖性增加，从0.194±0.024升至0.349±0.046 l/min（P < 0.01）。股动脉内输注L - NMMA完全抑制了LBF的这种增加。在两项研究中，AVGδ、LGU和全身葡萄糖处置率均随时间依赖性增加。胰岛素介导的血管舒张功能保持完整时的最大AVGδ低于受到抑制时（25.9±2.5 vs. 35.0±1.6 mg/dl，P < 0.001）。与受到抑制相比，胰岛素介导的血管舒张功能保持完整时达到最大AVGδ一半时的时间（T1/2）稍长（35.6±4.1 vs. 29.7±1.6分钟，P < 0.01）。在胰岛素介导的血管舒张功能保持完整和受到抑制时，最大LGU分别为93.9±26.8和57.2±11.6 mg/min（P < 0.005），T1/2 LGU分别为50.2±16.0和36.3±8.8分钟（P = 0.1）。因此，胰岛素介导的血管舒张在减缓胰岛素刺激葡萄糖摄取的时间进程方面有适度作用，但在增加骨骼肌中胰岛素刺激的葡萄糖摄取最大速率方面有显著作用。如在原发性高血压患者中观察到的胰岛素介导的血管舒张功能受损，可能至少部分解释了这些患者中观察到的胰岛素抵抗。
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