Onoue Takeshi, Goto Motomitsu, Tominaga Takashi, Sugiyama Mariko, Tsunekawa Taku, Hagiwara Daisuke, Banno Ryoichi, Suga Hidetaka, Sugimura Yoshihisa, Arima Hiroshi
Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan.
Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Showa-ku, Nagoya 466-8550, Japan.
Neurosci Lett. 2016 Apr 21;619:1-7. doi: 10.1016/j.neulet.2016.03.011. Epub 2016 Mar 9.
In the hypothalamus, several reports have implied that ROS mediate physiological effects of insulin. In this study, we investigated the mechanisms of insulin-induced ROS production and the effect of ROS on insulin signal transduction in mouse hypothalamic organotypic cultures. Insulin increased intracellular ROS, which were suppressed by NADPH oxidase inhibitor. H2O2 increased phospho-insulin receptor β (p-IRβ) and phospho-Akt (p-Akt) levels. Insulin-induced increases in p-IRβ and p-Akt levels were attenuated by ROS scavenger or NADPH oxidase inhibitor. Our data suggest that insulin-induced phosphorylation of IRβ and Akt is mediated via ROS which are predominantly produced by NADPH oxidase in mouse hypothalamus.
在下丘脑中,多项报告表明活性氧(ROS)介导胰岛素的生理作用。在本研究中,我们调查了胰岛素诱导ROS产生的机制以及ROS对小鼠下丘脑器官型培养物中胰岛素信号转导的影响。胰岛素增加细胞内ROS,这被NADPH氧化酶抑制剂所抑制。过氧化氢增加磷酸化胰岛素受体β(p-IRβ)和磷酸化Akt(p-Akt)水平。ROS清除剂或NADPH氧化酶抑制剂减弱了胰岛素诱导的p-IRβ和p-Akt水平升高。我们的数据表明,胰岛素诱导的IRβ和Akt磷酸化是通过ROS介导的,而ROS主要由小鼠下丘脑中的NADPH氧化酶产生。