INSULIN-RECEPTOR KINASE IN HUMAN SKELETAL-MUSCLE FROM OBESE SUBJECTS WITH AND WITHOUT NONINSULIN DEPENDENT DIABETES
INSULIN-RECEPTOR KINASE IN HUMAN SKELETAL-MUSCLE FROM OBESE SUBJECTS WITH AND WITHOUT NONINSULIN DEPENDENT DIABETES
复制标题
DOI：
10.1172/jci112958
复制
发表时间：
1987-05-01
影响因子：
15.9
通讯作者：
DOHM, GL
中科院分区：
文献类型：
--
作者：
CARO, JF;SINHA, MK;DOHM, GL
我们用部分纯化的肌肉活检胰岛素受体研究了肥胖组和非肥胖组的胰岛素受体的结构和功能。肥胖者的胰岛素结合减少是由于结合位点数减少所致，但肥胖者合并或不伴NIDDM时的胰岛素结合并无差异。通过亲和标记方法和β-亚基的电泳迁移率确定的受体的结构特征，与正常体重的受试者相比，肥胖者或NIDDM患者没有改变。此外，胰岛素刺激β-亚基自磷酸化的能力和磷酸化受体的磷酸氨基酸组成在所有组中都是相同的。然而，当肥胖与NIDDM相关时，使用Glu4：Tyr1作为外源性磷受体的肥胖者胰岛素受体激酶活性降低，没有任何明显的额外缺陷。因此，我们的数据支持这样的假设，即在肥胖者的肌肉中，胰岛素抵抗部分是由于胰岛素受体和胰岛素受体激酶活性增加所致。在非胰岛素依赖型糖尿病中，肌肉中的缺陷(S)可能位于胰岛素受体激酶的远端。
We have studied the structure and function of the insulin receptors in obese patients with and without noninsulin dependent diabetes mellitus (NIDDM) and in nonobese controls using partially purified receptors from muscle biopsies. Insulin binding was decreased in obesity due to reduced number of binding sites but no differences were observed in insulin binding between obese subjects with or without NIDDM. The structural characteristics of the receptors, as determined by affinity labeling methods and electrophoretic mobility of the .beta.-subunit, were not altered in obese or NIDDM compared to normal weight subjects. Furthermore, the ability of insulin to stimulate the autophosphorylation of the .beta.-subunit and the phosphoamino acid composition of the phosphorylated receptor were the same in all groups. However, insulin receptor kinase activity was decreased in obesity using Glu4:Tyr1 as exogenous phosphoacceptor without any appreciable additional defect when obesity was associated with NIDDM. Thus, our data are supportive of the hypothesis that in muscle of obese humans, insulin resistance is partially due to increased insulin receptors and insulin receptor kinase activity. In NIDDM the defect(s) in muscle is probably distal to the insulin receptor kinase.