Youd J M, Rattigan S, Clark M G
Division of Biochemistry, Medical School, University of Tasmania, Hobart, Australia.
Diabetes. 2000 Nov;49(11):1904-9. doi: 10.2337/diabetes.49.11.1904.
The vascular actions of insulin may contribute to the increase in glucose uptake by skeletal muscle. We have recently shown that when capillary recruitment by insulin is blocked in vivo, an acute state of insulin resistance is induced. Another agent that may have vascular effects is the inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha), which has been reported to play an important role in the insulin resistance of obesity, type 2 diabetes, and sepsis in both animals and humans. Thus, in the present study, we have investigated the effect of an intravenous 3-h TNF treatment (0.5 microg x h(1) x kg(-1)) in control and euglycemic-hyperinsulinemic-clamped (10 mU x min(-1) x kg(-1) for 2 h) anesthetized rats. Hind-leg glucose uptake, muscle uptake of 2-deoxyglucose (2-DG), femoral blood flow (FBF), vascular resistance (VR), and capillary recruitment as measured by metabolism of infused 1-methylxanthine (1-MX) were assessed. Insulin alone caused a significant (P < 0.05) increase in FBF (1.7-fold) and capillary recruitment (2.5-fold), with a significant decrease in VR. In addition, hind-leg glucose uptake was increased (fourfold), as was 2-DG uptake in the soleus and plantaris muscles. TNF completely prevented the insulin-mediated changes in FBF, VR, and capillary recruitment and significantly reduced (P < 0.05) the insulin-mediated increase in total hind-leg glucose uptake (by 61%) and muscle 2-DG uptake (by at least 50%). TNF alone had no significant effect on any of these variables. It is concluded that acute administration in vivo of TNF completely blocks the hemodynamic actions of insulin on rat skeletal muscle vasculature and blocks approximately half of the glucose uptake by muscle. It remains to be determined whether these two effects are interdependent.
胰岛素的血管作用可能有助于增加骨骼肌对葡萄糖的摄取。我们最近发现，当胰岛素介导的毛细血管募集在体内受到阻断时，会诱发急性胰岛素抵抗状态。另一种可能具有血管效应的物质是炎性细胞因子肿瘤坏死因子-α（TNF-α），据报道，它在动物和人类的肥胖、2型糖尿病及脓毒症的胰岛素抵抗中起重要作用。因此，在本研究中，我们研究了对麻醉的对照大鼠和血糖正常-高胰岛素钳夹（10 mU·min⁻¹·kg⁻¹，持续2小时）大鼠静脉输注TNF 3小时（0.5 μg·h⁻¹·kg⁻¹）的作用。评估了后肢葡萄糖摄取、肌肉对2-脱氧葡萄糖（2-DG）的摄取、股血流量（FBF）、血管阻力（VR）以及通过注入的1-甲基黄嘌呤（1-MX）代谢来测量的毛细血管募集情况。单独使用胰岛素可使FBF显著（P < 0.05）增加（1.7倍）和毛细血管募集增加（2.5倍），同时VR显著降低。此外，后肢葡萄糖摄取增加（四倍），比目鱼肌和跖肌中的2-DG摄取也增加。TNF完全阻止了胰岛素介导的FBF、VR和毛细血管募集的变化，并显著降低（P < 0.05）了胰岛素介导引起的后肢总葡萄糖摄取增加（61%）和肌肉2-DG摄取增加（至少50%）。单独使用TNF对这些变量均无显著影响。结论是，在体内急性给予TNF完全阻断了胰岛素对大鼠骨骼肌血管系统的血流动力学作用，并阻断了肌肉约一半的葡萄糖摄取。这两种作用是否相互依赖仍有待确定。
