Phosphotyrosine-containing proteins in the CNS of obese Zucker rats are decreased in the absence of changes in the insulin receptor.
Phosphotyrosine-containing proteins in the CNS of obese Zucker rats are decreased in the absence of changes in the insulin receptor.
复制标题
在胰岛素受体没有变化的情况下，肥胖 Zucker 大鼠中枢神经系统中的磷酸酪氨酸蛋白会减少。
DOI：
10.1159/000126395
复制
发表时间：
1993
影响因子：
4.1
通讯作者：
Moss,A
中科院分区：
文献类型：
--
作者：
Livingston,JN;Unger,JW;Moxley,RT;Moss,A
胰岛素受体的位置和数量及其相关的酪氨酸激酶活性已在LEAN(Fa/？)和肥胖(FA/FA)Zucker大鼠，使用免疫细胞化学(ICC)和生化程序。这些研究是与含有磷酸酪氨酸的蛋白(PY蛋白)的ICC和Western印迹分析一起进行的。ICC的结果显示，瘦身和肥胖的Zucker大鼠前脑区胰岛素受体的分布和含量相似。在海马区对该受体进行生化分析。使用凝集素纯化的受体提取物进行的胰岛素结合研究表明，瘦肉型和肥胖型动物的受体数量相似，激素结合亲和力相似。两组受体提取物的自动磷酸化研究没有发现胰岛素受体的酪氨酸激酶活性有任何差异。与正常的胰岛素受体结果相反，ICC检测到肥胖动物的海马区、梨状皮质和嗅球中的PY蛋白含量明显异常。这些脑区的神经元被一种抗PY蛋白的抗体染色减弱。此外，对肥胖大鼠海马区提取液的Western blotting显示，MR180和130kD两种蛋白的磷酸酪氨酸含量减少。这些发现指出了肥胖、胰岛素抵抗的Zucker大鼠中枢神经系统的一种以前未被认识到的变化。
The location and quantity of the insulin receptor and its associated tyrosine kinase activity have been examined in the forebrains of lean (Fa/?) and obese (fa/fa) Zucker rats using immunocytochemistry (ICC) and biochemical procedures. These studies were performed in conjunction with ICC and Western blot analysis of phosphotyrosine-containing proteins (PY-proteins). The results from ICC show a similar distribution and content for the insulin receptor among forebrain regions of lean and fatty Zucker rats. Biochemical analysis of the receptor was conducted on the hippocampus. Insulin binding studies using lectin-purified receptor extracts demonstrated similar receptor number and comparable hormone binding affinity for lean and obese animals. Auto-phosphorylation studies with the receptor extracts from the two groups did not find any differences in the tyrosine kinase activity of insulin receptors. In contrast to the normal findings with the insulin receptor, an abnormality in the obese animals was evident in the content of PY-proteins detected by ICC in the hippocampus, piriform cortex and olfactory bulb. Neurons in these brain regions showed a reduction in staining by an antibody against PY-proteins. Furthermore, Western blots of hippocampal extracts from obese rats demonstrated a reduction in phosphotyrosine content of two proteins of Mr180 and 130 kD. These findings point to a previously unrecognized alteration in the CNS of the obese, insulin-resistant Zucker rat.