The Site of Insulin Resistance in Acute Uremia
The Site of Insulin Resistance in Acute Uremia
复制标题
急性尿毒症胰岛素抵抗的部位
作者：
C. E. Mondon;C. Dolkas;G. Reaven
为了明确急性尿毒症大鼠葡萄糖耐受不良的机制，我们在双侧肾切除术后24小时进行了多项研究。与假手术大鼠相比，尿毒症大鼠静脉注射葡萄糖后的葡萄糖去除量显著减少（p < 0.001） （k = 2.1±0.03% vs. 5.1±0.2%）。葡萄糖给药后1至40分钟，尿毒症大鼠葡萄糖耐量的下降与胰岛素水平升高有关，这表明胰岛素抵抗是尿毒症大鼠葡萄糖去除减少的原因。为了确定胰岛素抵抗的部位，我们比较了从尿毒症大鼠和假手术大鼠获得的离体灌注肝脏和肌肉（后肢）制剂中胰岛素增强净葡萄糖摄取的能力。胰岛素对尿毒症大鼠灌注后肝脏葡萄糖流出的抑制作用至少与假手术大鼠相同，且在灌注胰岛素的最大水平（600 μ u /ml）和阈值（75 μ u /ml）均有抑制作用。与假手术大鼠相比，胰岛素（平均灌注液水平225 μ u /ml）促进尿毒症后肢葡萄糖摄取的能力明显降低。这些结果表明，急性尿毒症的胰岛素抵抗可能主要是由于骨骼肌胰岛素介导的葡萄糖摄取减少，而肝脏对胰岛素的敏感性没有降低。
In order to define the mechanism of glucose intolerance in acutely uremic rats, various studies were carried out 24 hours after bilateral nephrectomy. Glucose removal following intravenous glucose was significantly (p < 0.001) decreased in uremic rats compared with sham-operated rats (k = 2.1 ± 0.03 per cent vs. 5.1 ±0.2 per cent). This deterioration in glucose tolerance was associated with higher insulin levels in uremic rats from one to 40 minutes after glucose administration, suggesting that insulin resistance accounted for the decrease in glucose removal by uremic rats. To identify the site of the insulin resistance, we compared the ability of insulin to enhance net glucose uptake by isolated perfused liver and muscle (hindlimb) preparations obtained from uremic and shamoperated rats. Insulin suppressed glucose outflow from perfused livers of uremic rats at least as well as it did from livers of shamoperated rats, and suppression occurred at both maximal (> 600 μU./ml.) and threshold (75 μU./ml.) perfusate insulin levels. In contrast, there was a significant decrease in the ability of insulin (mean perfusate level = 225 μU./ml.) to enhance glucose uptake of perfused hindlimbs of uremic as compared with sham-operated rats. These results suggest that the insulin resistance of acute uremia may be due primarily to decreased insulin-mediated uptake of glucose by skeletal muscle without any decrease in sensitivity of the liver to insulin.