Galante P, Maerker E, Scholz R, Rett K, Herberg L, Mosthaf L, Häring H U
Institute for Diabetes Research, Munich, Germany.
Diabetologia. 1994 Jan;37(1):3-9. doi: 10.1007/BF00428770.
The genetically obese Zucker rat (fa/fa) is an animal model with severe insulin resistance of the skeletal muscle. We investigated whether a defect of insulin-dependent glucose transporter (GLUT 4) translocation might contribute to the pathogenesis of the insulin-resistant state. fa/fa rats, lean controls (Fa/Fa) as well as normal Wistar rats were injected intraperitoneally with insulin and were killed after 2 or 20 min, respectively. Subcellular fractions were prepared from hind-limb skeletal muscle and were characterized by determination of marker-enzyme activities and immunoblotting applying antibodies against alpha 1 Na+/K+ ATPase. The relative amounts of GLUT 1 and GLUT 4 were determined in the fractions by immunoblotting with the respective antibodies. Insulin induced an approximately two-fold increase of GLUT 4 in a plasma membrane and transverse tubule enriched fraction and a decrease in the low density enriched membrane fraction in all three groups of rats. There was a high individual variation in GLUT 4 translocation efficiency within the groups. However, no statistically significant difference was noted between the groups. No effect of insulin was detectable on the distribution of GLUT 1 or alpha 1 Na+K+ ATPase. The data suggest that skeletal muscle insulin resistance of obese Zucker rats is not associated with a lack of GLUT 4 translocation.
遗传性肥胖的 Zucker 大鼠（fa/fa）是一种具有严重骨骼肌胰岛素抵抗的动物模型。我们研究了胰岛素依赖性葡萄糖转运体（GLUT 4）转位缺陷是否可能导致胰岛素抵抗状态的发病机制。分别给 fa/fa 大鼠、瘦型对照大鼠（Fa/Fa）以及正常 Wistar 大鼠腹腔注射胰岛素，2 分钟或 20 分钟后将其处死。从后肢骨骼肌制备亚细胞组分，并通过测定标记酶活性以及使用抗α1 Na+/K+ ATP 酶抗体进行免疫印迹来进行表征。通过使用相应抗体进行免疫印迹，测定各组分中 GLUT 1 和 GLUT 4 的相对含量。胰岛素使所有三组大鼠中富含质膜和横管的组分中的 GLUT 4 增加约两倍，而使低密度富集膜组分中的 GLUT 4 减少。各组内 GLUT 4 转位效率存在高度个体差异。然而，各组之间未观察到统计学上的显著差异。未检测到胰岛素对 GLUT 1 或α1 Na+K+ ATP 酶分布有影响。数据表明，肥胖 Zucker 大鼠的骨骼肌胰岛素抵抗与 GLUT 4 转位缺乏无关。
