DECREASED EFFECT OF INSULIN TO STIMULATE SKELETAL-MUSCLE BLOOD-FLOW IN OBESE MAN - A NOVEL MECHANISM FOR INSULIN RESISTANCE
DECREASED EFFECT OF INSULIN TO STIMULATE SKELETAL-MUSCLE BLOOD-FLOW IN OBESE MAN - A NOVEL MECHANISM FOR INSULIN RESISTANCE
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DOI：
10.1172/jci114644
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发表时间：
1990-06-01
影响因子：
15.9
通讯作者：
BARON, AD
中科院分区：
文献类型：
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作者：
LAAKSO, M;EDELMAN, SV;BARON, AD
肥胖的特征是骨骼肌胰岛素介导的葡萄糖摄取率(IMGU)降低。由于IMGU等于穿过肌肉的动静脉血糖差(AVGd)和流入肌肉的血液的乘积，血流和/或组织活动(AVGd)的减少可能导致IMGU的下降。为了研究这个问题，我们研究了六个瘦身(体重68。+-。3公斤，平均+-。扫描电子显微镜)和6名肥胖者(94.+-。3公斤)男子。在大范围的血清胰岛素浓度范围内，使用正常血糖钳和腿平衡技术绘制了全身和腿部IMGU的胰岛素剂量-反应曲线。在消瘦和肥胖受试者中，全身IMGU、AVGd、血流量和腿部IMGU以剂量依赖的方式增加，所有参数的最大速率在肥胖者比消瘦受试者降低。肥胖受试者全身IMGU、腿部IMGU和AVGd的剂量-反应曲线右移，每个参数的ED50都比瘦受试者高两到三倍。腿部血流量较基础的2.7。+-增加了近两倍。0.2至4.4+-0.2 dl/min，P<；0.01，从2.5+-。0.3至4.4+-肥胖者01.4 dl/min，P<；0.01。S效应增加腿部血流量的ED50肥胖者(957pmol/升)是瘦人(266pmol/升)的四倍，P<；0.01。因此，肥胖患者胰岛素敏感性的降低不仅是由于胰岛素敏感组织中葡萄糖的低提取，也是由于这些组织的血流量减少。因此，在体内，胰岛素抵抗可能是由于组织水平的胰岛素作用缺陷和/或胰岛素增加胰岛素敏感组织血流量的血流动力学作用缺陷所致。
Obesity is characterized by decreased rates of skeletal muscle insulin-mediated glucose uptake (IMGU). Since IMGU equals the product of the arteriovenous glucose difference (AVGd) across muscle and blood flow into muscle, reduced blood flow and/or tissue activity (AVGd) can lead to decreased IMGU. To examine this issue, we studied six lean (weight 68 .+-. 3 kg, mean .+-. SEM) and six obese (94 .+-. 3 kg) men. The insulin dose-response curves for whole body and leg IMGU were constructed using the euglycemic clamp and leg balance techniques over a large range of serum insulin concentrations. In lean and obese subjects, whole body IMGU, AVGd, blood flow, and leg IMGU increased in a dose dependent fashion and maximal rates of all parameters were reduced in obese subjects compared to lean subjects. The dose-response curves for whole body IMGU, leg IMGU, and AVGd were right-shifted in obese subjects with an ED50 two- to threefold higher than that of lean subjects for each parameter. Leg blood flow increased approximately twofold from basal 2.7 .+-. 0.2 to 4.4 .+-. 0.2 dl/min in lean, P < 0.01, and from 2.5 .+-. 0.3 to 4.4 .+-. 0l.4 dl/min in obese subjects, P < 0.01. The ED50 for insulin''s effect to increase leg blood flow was about fourfold higher for obese (957 pmol/liter) than lean subjects (266 pmol/liter), P < 0.01. Therefore, decreased insulin sensitivity in human obesity is not only due to low glucose extraction in insulin-sensitive tissues but also to lower blood flow to these tissues. Thus, in vivo insulin resistance can be due to a defect in insulin action at the tissue level and/or a defect in insulin''s hemodynamic action to increase blood flow to insulin sensitive tissues.