The effect of diabetes, insulin, and the redox potential on leucine metabolism by isolated rat hemidiaphragm.
The effect of diabetes, insulin, and the redox potential on leucine metabolism by isolated rat hemidiaphragm.
复制标题
糖尿病、胰岛素和氧化还原电位对离体大鼠半膈亮氨酸代谢的影响。
作者：
M. Buse;H. Herlong;D. Weigand
在体外研究了正常和糖尿病大鼠膈肌对亮氨酸的氧化作用。用链脲佐菌素使大鼠患糖尿病。在与0.1 mM [1- 14 C]亮氨酸孵育期间，糖尿病大鼠的横膈膜产生的14 CO2比对照肌肉多约50%。在有或无葡萄糖孵育期间以及在存在或不存在血浆氨基酸完全补体的情况下观察到这一点。培养前糖尿病大鼠半侧膈肌组织水中亮氨酸的浓度高于对照组。在60分钟孵育结束时，亮氨酸的比活性在糖尿病和对照肌肉中没有显著差异，表明增加的14 CO2产生代表亮氨酸氧化的刺激。糖尿病大鼠的半横膈膜在孵育过程中比对照组肌肉释放更多的亮氨酸到培养基中。糖尿病在体外对亮氨酸氧化的刺激作用在处死前通过胰岛素治疗是可逆的。在含有葡萄糖的培养基中加入5 mM丙酮酸盐可抑制对照组肌肉中[14 C]亮氨酸产生14 CO2，但可刺激糖尿病大鼠膈肌中亮氨酸的氧化。亮氨酸氧化的糖尿病大鼠的半横膈膜显着刺激的电子受体，0.02 mM的亚甲基蓝，这表明NADH/NAD的比例可能是糖尿病大鼠的肌肉中的支链氨基酸氧化的限速，但不是在肌肉的控制。我们认为，加速氧化的支链氨基酸的肌肉可能发挥作用，在加速肌肉蛋白质catenorization和胰岛素缺乏时发展。细胞氧化还原电位对支链氨基酸氧化的抑制作用可能在长时间禁食期间蛋白质催化剂的最终减速中发挥作用。
The oxidation of leucine by hemidiaphragms of control and diabetic rats was studied in vitro. Rats were rendered diabetic with streptozotocin. Hemidiaphragms of diabetic rats produced approximately 50% more 14CO2 during incubation with 0.1 mM [1-14C]leucine than did control muscles. This was observed during incubation with or without glucose and in the presence or absence of a full complement of plasma amino acids. The concentration of leucine in the tissue water of hemidiaphragms from diabetic rats was greater than that in the control muscles before incubation. The specific activity of leucine at the end of 60 min incubation was not significantly different in diabetic and control muscles, indicating that the increased 14CO2 production represented stimulation of leucine oxidation. Hemidiaphragms of diabetic rats released more leucine into the medium during incubation than did control muscles. The stimulating effect of diabetes on leucine oxidation in vitro was reversible by insulin therapy prior to sacrifice. The addition of 5 mM pyruvate to a medium containing glucose inhibited 14CO2 production from [14C]leucine in control muscles, but stimulated leucine oxidation by hemidiaphragms of diabetic rats. Leucine oxidation by hemidiaphragms of diabetic rats was markedly stimulated by the addition of an electron acceptor, 0.02 mM methylene blue, suggesting that the NADH/NAD ratio may be rate-limiting for branched chain amino acid oxidation in muscles of diabetic rats, but not in muscles of controls. We suggest that the accelerated oxidation of branched chain amino acids by muscles may play a role in the acceleration of the muscle protein catabolism and gluconeogenesis which develop during insulin deficiency. The restraining effect of the cellular redox potential on branched chain amino acid oxidation may play a role in the eventual deceleration of protein catabolism during a prolonged fast.