Davidson M B, Bouch C, Venkatesan N, Karjala R G
Department of Medicine, Cedars-Sinai Medical Center, University of California at Los Angeles 90048.
Am J Physiol. 1994 Dec;267(6 Pt 1):E808-13. doi: 10.1152/ajpendo.1994.267.6.E808.
This study was undertaken to determine if glucose toxicity in normal rats caused decreased whole body insulin-stimulated glucose disposal and in vivo impaired muscle glucose transport and, if so, whether it was mediated by changes in GLUT-4 content or tissue distribution. Rats were infused with 50% dextrose for 48 h after which they were clamped and injected with 2-deoxy-D-[3H]glucose. Hindlimb muscles were removed for measurement of uptake of radioactivity (glucose transport) and GLUT-4 levels in total, plasma and internal membrane fractions. Dextrose infusions caused significant hyperglycemia [15.5 +/- 1.4 vs. 6.7 +/- 0.3 (SE) mM], hyperinsulinemia [678 +/- 108 vs. 168 +/- 42 (SE) pM], and depressed insulin-mediated whole body glucose disposal [12.8 +/- 2.0 vs. 47.0 +/- 10.6 (SE) mg glucose.kg-1.min-1.pmol insulin-1.1(-1) x 10(3)]. Muscle glucose transport (ng.min-1.mg tissue-1) was significantly decreased in biceps (4.0 +/- 0.6 vs. 13.4 +/- 2.5), gastrocnemius (4.6 +/- 1.1 vs. 12.9 +/- 2.2), and plantaris (5.5 +/- 0.7 vs. 17.5 +/- 3.6) muscles compared with saline-infused rats. The difference in the soleus muscle (13.2 +/- 1.6 vs. 19.4 +/- 2.7) did not quite reach statistical significance. There were no differences in total, plasma, or internal membrane GLUT-4 content between the two groups. It is concluded that glucose toxicity causes impaired insulin-stimulated glucose transport, probably due to decreased activity of GLUT-4.
本研究旨在确定正常大鼠体内的葡萄糖毒性是否会导致全身胰岛素刺激的葡萄糖处置减少以及体内肌肉葡萄糖转运受损，如果是这样，其是否由葡萄糖转运蛋白4（GLUT-4）含量或组织分布的变化介导。给大鼠输注50%葡萄糖48小时，之后对其进行钳夹并注射2-脱氧-D-[3H]葡萄糖。取出后肢肌肉以测量放射性摄取（葡萄糖转运）以及总组分、血浆组分和内膜组分中的GLUT-4水平。葡萄糖输注导致显著的高血糖[15.5±1.4 vs. 6.7±0.3（标准误）mM]、高胰岛素血症[678±108 vs. 168±42（标准误）pM]，并使胰岛素介导的全身葡萄糖处置降低[12.8±2.0 vs. 47.0±10.6（标准误）mg葡萄糖·kg-1·min-1·pmol胰岛素-1·1(-1)×10(3)]。与输注生理盐水的大鼠相比，二头肌（4.0±0.6 vs. 13.4±2.5）、腓肠肌（4.6±1.1 vs. 12.9±2.2）和跖肌（5.5±0.7 vs. 17.5±3.6）的肌肉葡萄糖转运（ng·min-1·mg组织-1）显著降低。比目鱼肌的差异（13.2±1.6 vs. 19.4±2.7）未达到统计学显著性。两组之间的总GLUT-4含量、血浆GLUT-4含量或内膜GLUT-4含量均无差异。得出的结论是，葡萄糖毒性导致胰岛素刺激的葡萄糖转运受损，可能是由于GLUT-4活性降低所致。
