Insulin resistance in uremia. Characterization of insulin action, binding, and processing in isolated hepatocytes from chronic uremic rats.
Insulin resistance in uremia. Characterization of insulin action, binding, and processing in isolated hepatocytes from chronic uremic rats.
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尿毒症的胰岛素抵抗。
DOI：
10.1172/jci110816
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发表时间：
1983
期刊：
影响因子：
--
通讯作者：
J. Caro
中科院分区：
文献类型：
--
作者：
J. Kauffman;J. Caro
我们已经在大鼠中开发了一种导致可预测程度的严重尿毒症的模型，以研究肝脏在尿毒症胰岛素抵抗状态中的作用。尿毒症动物血糖正常，血清免疫反应性胰岛素增加时，与他们的配对喂养对照。胰岛素的作用，结合，内化和降解的特点，新鲜分离的肝细胞尿毒症动物，假手术配对喂养，和自由。美联储控制。氨基异丁酸（AIB）摄取的基础率增加，从尿毒症和配对喂养的对照大鼠的肝细胞。然而，虽然尿毒症动物的肝细胞对胰岛素的AIB摄取是难治性的，但在基础AIB摄取以上的绝对增量方面，成对喂养和随意喂养的肝细胞没有显著差异。研究的任何胰岛素浓度下的动物。与自由进食相比，在24 ℃下，在研究的每个胰岛素浓度下，尿毒症大鼠肝细胞中的125 I-胰岛素结合率较高。对照在37 ℃下研究了125 I-胰岛素与细胞和膜结合或内化的组分结合的时间过程。在膜结合125 I-胰岛素在37 ℃的增加也存在于尿毒症动物的肝细胞。所有动物组的肝细胞均内化了相同比例的膜结合125 I-胰岛素。细胞外和受体介导的125 I-胰岛素降解在质膜和内化后，在37 ℃下通过凝胶色谱法进行了研究。在三个隔室中，尿毒症大鼠肝细胞中125 I-胰岛素降解速率延迟和降低。我们的结论是：（a）在慢性尿毒症中，肝脏对胰岛素的AIB摄取是难治性的。(b)尿毒症大鼠肝脏的胰岛素抵抗不是由于胰岛素结合或内化缺陷。(c)尽管高水平的循环免疫反应性胰岛素，尿毒症大鼠的肝细胞并没有显示出预期的“下调”的胰岛素受体或胰岛素降解率增加。这些研究进一步强调了结合后事件在调节胰岛素结合和降解中的主要作用。关于肝脏中胰岛素代谢的协调步骤如何在病理状态下被破坏的机制目前尚不清楚。
We have developed a model in the rat that leads to a predictable degree of severe uremia to study the role of the liver in the insulin-resistant state of uremia. The uremic animals were euglycemic and had increased serum immunoreactive insulin when compared with their pair-fed controls. Insulin action, binding, internalization, and degradation were characterized in freshly isolated hepatocytes from uremic animals, sham-operated pair-fed, and ad lib.-fed controls. The basal rate of aminoisobutyric acid (AIB) uptake was increased in hepatocytes from both uremic and pair-fed control rats. However, while hepatocytes from uremic animals were refractory to insulin with regard to AIB uptake, there was no significant difference in the absolute increment above basal AIB uptake by hepatocytes from pair-fed and fed ad lib. animals at any insulin concentration studied. 125I-Insulin binding at 24 degrees C was higher in hepatocytes from uremic rats at every insulin concentration studied when compared with fed ad lib. controls. The time course of 125I-insulin binding to the cell and to the fractions that were membrane bound or internalized were studied at 37 degrees C. An increase in membrane-bound 125I-insulin at 37 degrees C was present also in hepatocytes from uremic animals. The same fraction of membrane-bound 125I-insulin was internalized in hepatocytes from all groups of animals. Extracellular and receptor-mediated 125I-insulin degradation at the plasma membrane and after internalization was studied at 37 degrees C by gel chromatography. There was a delayed and decreased rate of 125I-insulin degradation in hepatocytes from uremic rats in the three compartments. We conclude: (a) In chronic uremia the liver is refractory to insulin with regard to AIB uptake. (b) Insulin resistance in uremic rat liver is not due to defects in insulin binding or internalization. (c) Despite the high level of circulating immunoreactive insulin, hepatocytes from uremic rats did not show the expected "down regulation" of their insulin receptors or an increased rate of insulin degradation. These studies further emphasize the primary role of postbinding events in the regulation of insulin binding and degradation. The mechanism as to how the coordinated steps of insulin metabolism in the liver are disrupted in a pathological state is presently unknown.
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糖皮质激素诱导的胰岛素抵抗：结合后事件在新鲜分离的大鼠肝细胞和原代培养物中胰岛素结合、作用和降解调节中的重要性。
DOI：
10.1172/jci110526
发表时间：
1982
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Caro,JF;Amatruda,JM
通讯作者：
Amatruda,JM
胰岛素结合、作用和降解之间的功能关系。
DOI：
--
发表时间：
1980
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Caro,JF;Amatruda,JM
通讯作者：
Amatruda,JM
胰岛素由肝脏加工。
DOI：
--
发表时间：
1982
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Caro,JF;Muller,G;Glennon,JA
通讯作者：
Glennon,JA
影响因子：
15.9
作者：
DEFRONZO, RA;ALVESTRAND, A;WAHREN, J
通讯作者：
WAHREN, J
禁食、链脲佐菌素糖尿病大鼠和老年自发性肥胖大鼠分离肝细胞中的胰岛素作用和结合。
DOI：
10.1042/bj1880839
发表时间：
1980
期刊：
The Biochemical journal
影响因子：
--
作者：
Cech,JM;FreemanJr,RB;Caro,JF;Amatruda,JM
通讯作者：
Amatruda,JM