Maillet C, Garber A J
Am J Clin Nutr. 1980 Jul;33(7):1343-53. doi: 10.1093/ajcn/33.7.1343.
The kinetics and factors regulating acid release were studied in epitrochlaris preparations of control and chronically uremic rats. These data were correlated with abnormal glucose and glucose precursor kinetics of azotemic patients and the impact of hemodialysis on these precursor-product interrelationships. In chronically uremic rat skeletal muscle, a subsensitivity to catecholamines was evident. A 1000-fold greater concentration of epinephrine was required in uremic muscle to inhibit alanine release compared to control preparations. The dose-response curve for cAMP formation stimulated by epinephrine was shifted 1 log unit to the right in uremic muscle and adenylyl cyclase stimulation by epinephrine was shifted 1 log unit. Using simultaneous primed-injection-continuous infusions [U-14C]-alanine and [2-3H]glucose, rates of metabolite turnovers were calculated from the plateau portions of the specific activity curves. In 14 azotemic patients, alanine and glucose turnover rates were found to be increased 276 and 154%, respectively, over that of the control group of 17 subjects. Glucose production was found to be 3-fold greater. Hemodialysis decreased alanine turnover by 35% and glucose production by 19%. However, glucose turnover was not affected by dialysis. Although the percentage of glucose produced from alanine approached normal levels, the percent of alanine used for gluconeogenesis increased 60%. These studies demonstrate that abnormal carbohydrate metabolism in uremia is a result of multiple factors. Diminished response of adenylyl cyclase and decreased levels of cAMP contributes to, but does not entirely account for, increased amino acid release. The increased alanine synthesis in skeletal muscle supports glucose overproduction found in chronic azotemia. Hemodialysis ameliorates but does not fully normalize glucose and alanine metabolism and may actually introduce additional abnormalities.
在对照大鼠和慢性尿毒症大鼠的肱三头肌制备物中研究了酸释放的动力学及调节因素。这些数据与氮质血症患者异常的葡萄糖和葡萄糖前体动力学以及血液透析对这些前体 - 产物相互关系的影响相关。在慢性尿毒症大鼠骨骼肌中，对儿茶酚胺的敏感性降低是明显的。与对照制备物相比，尿毒症肌肉中抑制丙氨酸释放所需的肾上腺素浓度要高1000倍。肾上腺素刺激cAMP形成的剂量 - 反应曲线在尿毒症肌肉中向右移动1个对数单位，肾上腺素对腺苷酸环化酶的刺激也向右移动1个对数单位。使用同时的初剂量注射 - 连续输注[U - 14C] - 丙氨酸和[2 - 3H] - 葡萄糖，从比活性曲线的平稳部分计算代谢物周转率。在14例氮质血症患者中，发现丙氨酸和葡萄糖周转率分别比17名受试者的对照组增加了276％和154％。发现葡萄糖生成增加了3倍。血液透析使丙氨酸周转率降低35％，葡萄糖生成降低19％。然而，葡萄糖周转率不受透析影响。虽然由丙氨酸产生的葡萄糖百分比接近正常水平，但用于糖异生的丙氨酸百分比增加了60％。这些研究表明，尿毒症中碳水化合物代谢异常是多种因素的结果。腺苷酸环化酶反应减弱和cAMP水平降低促成但不能完全解释氨基酸释放增加。骨骼肌中丙氨酸合成增加支持了慢性氮质血症中发现的葡萄糖过度生成。血液透析改善但不能完全使葡萄糖和丙氨酸代谢正常化，实际上可能会引入额外的异常情况。
