STUDIES ON THE MECHANISM OF INSULIN RESISTANCE IN THE LIVER FROM HUMANS WITH NONINSULIN-DEPENDENT DIABETES - INSULIN ACTION AND BINDING IN ISOLATED HEPATOCYTES, INSULIN-RECEPTOR STRUCTURE, AND KINASE-ACTIVITY
STUDIES ON THE MECHANISM OF INSULIN RESISTANCE IN THE LIVER FROM HUMANS WITH NONINSULIN-DEPENDENT DIABETES - INSULIN ACTION AND BINDING IN ISOLATED HEPATOCYTES, INSULIN-RECEPTOR STRUCTURE, AND KINASE-ACTIVITY
复制标题
DOI：
10.1172/jci112558
复制
发表时间：
1986-07-01
影响因子：
15.9
通讯作者：
SINHA, MK
中科院分区：
文献类型：
--
作者：
CARO, JF;ITTOOP, O;SINHA, MK
我们已经开发出一种方法，以分离胰岛素反应的人肝细胞从术中肝活检研究胰岛素的作用和阻力man. Hepatocytes肥胖患者的非胰岛素依赖型糖尿病的肝细胞耐最大的胰岛素浓度，和那些从肥胖对照组次最大的胰岛素浓度相比，非肥胖对照。胰岛素结合/细胞数在所有组中相似。然而，在两个肥胖组中，单位表面积的胰岛素结合率降低，因为他们的肝细胞更大。此外，糖尿病患者的洗涤剂可提取受体池进一步减少。亲和标记法测定各组胰岛素受体均未发生改变。然而，胰岛素刺激的胰岛素受体激酶活性在糖尿病患者中降低。因此，在肥胖症中，表面结合减少可以解释对次最大胰岛素浓度的抵抗。在糖尿病中，胰岛素刺激的蛋白激酶活性降低和细胞内受体池减少可以解释人肝脏中胰岛素作用的胰岛素结合后缺陷。
We have developed a method to isolate insulin-responsive human hepatocytes from an intraoperative liver biopsy to study insulin action and resistance in man. Hepatocytes from obese patients with noninsulin-dependent diabetes were resistant to maximal insulin concentration, and those from obese controls to submaximal insulin concentration in comparison to nonobese controls. Insulin binding per cell number was similar in all groups. However, insulin binding per surface area was decreased in the two obese groups because their hepatocytes were larger. In addition, the pool of detergent-extractable receptor was further decreased in diabetics. Insulin receptors in all groups were unaltered as determined by affinity-labeling methods. However, insulin-stimulated insulin receptor kinase activity was decreased in diabetics. Thus, in obesity, decreased surface binding could explain resistance to submaximal insulin concentrations. In diabetes, diminished insulin-stimulated protein kinase activity and decreased intracellular pool of receptors could provide an explanation for postinsulin-binding defect(s) of insulin action in human liver.