Maternal protein restriction induces alterations in insulin signaling and ATP sensitive potassium channel protein in hypothalami of intrauterine growth restriction fetal rats.
Maternal protein restriction induces alterations in insulin signaling and ATP sensitive potassium channel protein in hypothalami of intrauterine growth restriction fetal rats.
复制标题
母体蛋白质限制诱导宫内生长受限胎鼠下丘脑胰岛素信号和 ATP 敏感钾通道蛋白的改变
DOI：
10.3164/jcbn.12-28
复制
发表时间：
2013-01
影响因子：
2.4
通讯作者：
Yuan Z
中科院分区：
文献类型：
--
作者：
Liu X;Qi Y;Gao H;Jiao Y;Gu H;Miao J;Yuan Z
众所周知，宫内生长受限导致成年后胰岛素抵抗和2型糖尿病的发展。为了研究这种“代谢印记”现象背后的机制，我们检测了母体营养不良对宫内生长受限胎儿下丘脑胰岛素信号通路和ATP敏感性钾通道表达的影响。采用母体低蛋白饮食建立宫内生长受限大鼠模型。采用Western blot和真实的时间PCR检测孕20 d大鼠下丘脑胰岛素信号分子和KATP蛋白的表达和活化水平。宫内生长受限胎儿下丘脑胰岛素受体底物2和磷脂酰肌醇3 '-激酶p85α的酪氨酸磷酸化水平明显降低。下丘脑ATP敏感性钾通道亚单位磺酰脲受体1也下调，磺酰脲受体1传递胰岛素信号。此外，胎儿宫内生长受限的肝脏中的新生血管生成酶的丰度增加，尽管磺酰脲受体1和新生血管生成酶之间没有观察到相关性。我们的数据表明，异常的宫内环境损害下丘脑中的胰岛素信号，这些改变在生命早期可能有助于宫内生长受限胎儿向成人代谢紊乱的易感性。
It is well recognized that intrauterine growth restriction leads to the development of insulin resistance and type 2 diabetes mellitus in adulthood. To investigate the mechanisms behind this ”metabolic imprinting” phenomenon, we examined the impact of maternal undernutrition on insulin signaling pathway and the ATP sensitive potassium channel expression in the hypothalamus of intrauterine growth restriction fetus. Intrauterine growth restriction rat model was developed through maternal low protein diet. The expression and activated levels of insulin signaling molecules and KATP protein in the hypothalami which were dissected at 20 days of gestation, were analyzed by western blot and real time PCR. The tyrosine phosphorylation levels of the insulin receptor substrate 2 and phosphatidylinositol 3'-kinase p85α in the hypothalami of intrauterine growth restriction fetus were markedly reduced. There was also a downregulation of the hypothalamic ATP sensitive potassium channel subunit, sulfonylurea receptor 1, which conveys the insulin signaling. Moreover, the abundances of gluconeogenesis enzymes were increased in the intrauterine growth restriction livers, though no correlation was observed between sulfonylurea receptor 1 and gluconeogenesis enzymes. Our data suggested that aberrant intrauterine milieu impaired insulin signaling in the hypothalamus, and these alterations early in life might contribute to the predisposition of the intrauterine growth restriction fetus toward the adult metabolic disorders.
登录
查看更多内容
影响因子：
4.8
作者：
Seghers, V;Nakazaki, M;Bryan, J
通讯作者：
Bryan, J
影响因子：
8.2
作者：
Devaskar, Sherin U.;Thamotharan, Manikkavasagar
通讯作者：
Thamotharan, Manikkavasagar
影响因子：
8.2
作者：
Ozanne, S. E.;Jensen, C. B.;Vaag, A. A.
通讯作者：
Vaag, A. A.
DOI：
10.1152/ajpregu.00206.2004
发表时间：
2005-02-01
影响因子：
2.8
作者：
Fernandez-Twinn, DS;Wayman, A;Ozanne, SE
通讯作者：
Ozanne, SE
影响因子：
7.7
作者：
Niswender, KD;Morrison, CD;Schwartz, MW
通讯作者：
Schwartz, MW