Delayed transcapillary transport of insulin to muscle interstitial fluid in obese subjects
Delayed transcapillary transport of insulin to muscle interstitial fluid in obese subjects
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DOI：
10.2337/diabetes.51.9.2742
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发表时间：
2002-09-01
期刊：
影响因子：
7.7
通讯作者：
Lönnroth, P
中科院分区：
文献类型：
--
作者：
Sjöstrand, M;Gudbjörnsdottir, S;Lönnroth, P
胰岛素抵抗的受试者胰岛素起效较慢，其潜在机制尚未确定。为了评估毛细血管转运延迟是否是外周胰岛素抵抗的一部分，我们跟踪观察了肥胖胰岛素抵抗患者和对照组血浆和肌肉间质液中输入的胰岛素和菊粉的动力学。对10名瘦削男性和10名肥胖男性(BMI24+/-0.8vs.32+/-0.8 kg/m(2)，p<；0.001)进行高胰岛素-正常血糖钳夹试验。M(-2)。Min(-1))与菊粉输注相结合。采用前臂动静脉置管法和肱二头肌微透析法测定血浆胰岛素和菊粉浓度，并用静脉闭塞血流图测定前臂血流量。肥胖组的稳态葡萄糖输注率显著降低，而且胰岛素(对照组达到一半最大浓度的时间[T-1/2]72+/-6比46+/-6分钟，P<；0.05)和菊糖(T-1/2 83+/-3比53+/-7分钟，P<；0.01)延迟出现。此外，肥胖受试者的胰岛素作用开始时间延迟(对照组为T-1/2 70+/-9比45+/-5分钟，P<；0.05)，他们的前臂血流速度显著降低。这些结果表明，胰岛素和菊糖从血浆到肌肉间质液的跨毛细血管转运延迟，胰岛素作用的开始延迟。
Insulin-resistant subjects have a slow onset of insulin action, and the underlying mechanism has not been determined. To evaluate whether a delayed transcapillary transport is part of the peripheral insulin resistance, we followed the kinetics of infused insulin and inulin in plasma and muscle interstitial fluid in obese insulin-resistant patients and control subjects. A total of 10 lean and 10 obese men (BMI 24 +/- 0.8 vs. 32 +/- 0.8 kg/m(2), p < 0.001) was evaluated during a hyperinsulinemic-euglycemic clamp (insulin infusion rate 120 mU . m(-2) . min(-1)) combined with an inulin infusion. Measurements of insulin and inulin in plasma were taken by means of arterial-venous catheterization of the forearm and microdialysis in brachioradialis muscle combined with forearm blood flow measurements with vein occlusion pletysmography. The obese subjects had a significantly lower steady-state glucose infusion rate and, moreover, demonstrated a delayed appearance of insulin (time to achieve half-maximal concentration [T-1/2] 72 +/- 6 vs. 46 +/- 6 min in control subjects, P < 0.05) as well as inulin (T-1/2 83 +/- 3 vs. 53 +/- 7 min, P < 0.01) in the interstitial fluid. Also, the obese subjects had a delayed onset of insulin action (T-1/2 70 +/- 9 vs. 45 +/- 5 min in control subjects, P < 0.05), and their forearm blood flow rate was significantly lower. These results demonstrate a delayed transcapillary transport of insulin and inulin from plasma to the muscle interstitial fluid and a delayed onset of insulin action in insulin-resistant obese subjects.