Clark A S, Mitch W E
J Clin Invest. 1983 Sep;72(3):836-45. doi: 10.1172/JCI111054.
Acute renal failure (ARF) in rats is associated with increased amino acid release from peripheral tissues and insulin resistance. To study whether abnormal protein and carbohydrate metabolism are linked in ARF, the effects of insulin on net muscle protein degradation (T) and on glucose uptake were measured in the perfused hindquarters of paired ARF and sham-operated (SO) rats. The basal rate of T increased 40% after 24 and 98% after 48 h of ARF. Insulin was less effective in decreasing T in ARF (-79% SO vs. -22% ARF 24 h and -64% SO vs. -23% ARF 48 h; P less than 0.01). Protein synthesis (PS) and protein degradation (PD) were measured independently in incubated epitrochlearis muscles; the increase in T after 24 h of ARF was due specifically to increased PD, while PS was unchanged. At this stage, insulin was less effective in decreasing PD in ARF (-10% ARF vs. -23% SO; P less than 0.02), although PS responded normally. After 48 h of ARF, the further increment in T was caused by the additional appearance of depressed basal and insulin-stimulated PS. This was confirmed in the perfused hindquarter (26 +/- 3 ARF vs. 38 +/- 3 SO, basal; 54 +/- 5 ARF vs 73 +/- 7 SO, insulin-stimulated, nmol phenylalanine/g per h; P less than 0.05). Although basal glucose uptake by hindquarters of ARF and SO rats was comparable, insulin-stimulated glucose uptake was 33% less at 24 and 44% less after 48 h of ARF. After 48 h of ARF, lactate and alanine release were increased and net glycogen synthesis in muscle was depressed. These abnormalities were even more apparent in the presence of insulin. Inefficient glucose utilization, estimated as the ratio of lactate release to glucose uptake, was correlated with T (r = +0.78; P less than 0.001). In conclusion, after 24 h of ARF, both increased PD and altered glucose utilization could be detected. After 48 h of ARF, T increased further because PS was depressed. At this time, glucose utilization was clearly abnormal and the results suggest that abnormal net protein degradation in ARF may be a consequence of defective glucose utilization.
大鼠急性肾衰竭（ARF）与外周组织氨基酸释放增加及胰岛素抵抗有关。为研究ARF中异常的蛋白质和碳水化合物代谢是否相关，在成对的ARF大鼠和假手术（SO）大鼠的灌注后肢中，测定了胰岛素对净肌肉蛋白质降解（T）和葡萄糖摄取的影响。ARF 24小时后，T的基础速率增加了40%，48小时后增加了98%。胰岛素降低ARF中T的效果较差（24小时时，SO组降低79%，ARF组降低22%；48小时时，SO组降低64%，ARF组降低23%；P<0.01）。在孵育的肱三头肌中分别测量蛋白质合成（PS）和蛋白质降解（PD）；ARF 24小时后T的增加 specifically 是由于PD增加，而PS未改变。在此阶段，胰岛素降低ARF中PD的效果较差（ARF组降低10%，SO组降低23%；P<0.02），尽管PS反应正常。ARF 48小时后，T的进一步增加是由于基础和胰岛素刺激的PS降低的额外出现。这在灌注后肢中得到证实（基础状态下，ARF组为26±3，SO组为38±3；胰岛素刺激后，ARF组为54±5，SO组为73±7，nmol苯丙氨酸/g每小时；P<0.05）。尽管ARF大鼠和SO大鼠后肢的基础葡萄糖摄取相当，但ARF 24小时后胰岛素刺激的葡萄糖摄取减少了33%，48小时后减少了44%。ARF 48小时后，乳酸和丙氨酸释放增加，肌肉中的净糖原合成降低。在胰岛素存在的情况下，这些异常更加明显。以乳酸释放与葡萄糖摄取的比值估算的低效葡萄糖利用与T相关（r = +0.78；P<0.001）。总之，ARF 24小时后，可检测到PD增加和葡萄糖利用改变。ARF 48小时后，T进一步增加是因为PS降低。此时，葡萄糖利用明显异常，结果表明ARF中异常的净蛋白质降解可能是葡萄糖利用缺陷的结果。
