Role of Neuronal Network System in Development of the Metabolic Syndrome

神经元网络系统在代谢综合征发生中的作用

• 批准号: 20390252
• 负责人: KATAGIRI Hideki
• 金额: $ 11.98万
• 依托单位: Tohoku University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20390252/
• 关键词: 糖尿病; メタボリックシンドローム; 肥満; 臓器間ネットワーク; インスリン; 膵β細胞

We have recently discovered that neuronal networks among organs/tissues play important roles in maintaining metabolic homeostasis in the whole body. In this study, we examined how the inter-organ neuronal networks contribute to the development of the metabolic syndrome. First, we found that hepatic ERK activation induced insulin hypersecretion and pancreatic beta cell proliferation. This liver-to-pancreas coordination is mediated by a novel neuronal network, consisting the splanchnic afferents and vagal efferents. Furthermore, this neuronal network is involved in obesity-induced hyperinsulinemia. In addition, we have found that another neuronal network originating in hepatic PPARgamma expression causes hypertension associated with obesity. Thus, this study has revealed the mechanisms underlying obesity-induced hyperinsulinemia and hypertension, which are major features of the metabolic syndrome. The mechanisms involve two types of inter-organ metabolic networks, which are potential therapeutic targets for the metabolic syndrome.

我们最近发现，器官/组织之间的神经元网络在维持全身代谢动态平衡方面发挥着重要作用。在这项研究中，我们研究了器官间神经元网络如何促进代谢综合征的发展。首先，我们发现肝脏ERK激活诱导胰岛素高分泌和胰岛β细胞增殖。这种肝到胰腺的协调是由一个新的神经网络介导的，该网络由内脏传入和迷走神经传出组成。此外，这种神经网络与肥胖引起的高胰岛素血症有关。此外，我们还发现，另一个起源于肝脏PPAR-γ表达的神经元网络会导致与肥胖相关的高血压。因此，这项研究揭示了肥胖引起的高胰岛素血症和高血压的机制，这是代谢综合征的主要特征。这种机制涉及两种类型的器官间代谢网络，它们是代谢综合征的潜在治疗靶点。

项目成果

Peginterferon (PEG-IFN) plus Ribavirin Combination Therapy, but neither Interferon nor PGE-IFN Alone, Apparently Induced Type 1 Diabetes in a Patient with Chronic Hepatitis C

聚乙二醇干扰素 (PEG-IFN) 加利巴韦林联合治疗，但单独使用干扰素或 PGE-IFN 显然不会诱发慢性丙型肝炎患者患 1 型糖尿病

• 发表时间: 2009
• 期刊: Internal Medicine 48
• 作者: Ogihara T;Katagiri H;Yamada T.;Kudo H;Imai J;Ishigaki Y;Hinokio Y;Yamagiwa Y;Ueno Y;Shimosegawa T;Oka Y.
• 通讯作者: Oka Y.

Regulation of Pancreatic β Cell Mass by Neuronal Signals from the Liver

• DOI: 10.1126/science.1163971
• 发表时间: 2008-11-21
• 期刊: SCIENCE
• 影响因子: 56.9
• 作者: Imai, Junta;Katagiri, Hideki;Oka, Yoshitomo
• 通讯作者: Oka, Yoshitomo

4F2hc stabilizes GLUT1 protein and increases glucose transport activity

• DOI: 10.1152/ajpcell.00416.2010
• 发表时间: 2011-05-01
• 期刊: AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
• 影响因子: 5.5
• 作者: Ohno, Haruya;Nakatsu, Yusuke;Asano, Tomoichiro
• 通讯作者: Asano, Tomoichiro

Increased E4 Activity in Mice Leads to Ubiquitin-containing Aggregates and Degeneration of Hypothalamic Neurons Resulting in Obesity

• DOI: 10.1074/jbc.m110.105841
• 发表时间: 2010-05-14
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Susaki, Etsuo;Kaneko-Oshikawa, Chie;Nakayama, Keiichi I.
• 通讯作者: Nakayama, Keiichi I.

Impact of Plasma Oxidized LDL Removal on Atherosclerosis

血浆氧化 LDL 去除对动脉粥样硬化的影响

• 发表时间: 2008
• 期刊: Circulation 118(1)
• 作者: Ishigaki Y;Katagiri H;Gao J;Yamada T;Imai J;Uno K;Hasegawa Y;Kaneko K;Ogihara T;Ishihara H;Sato Y;Takikawa K;Nishimichi N;Matsuda H;Sawamura T;Oka Y
• 通讯作者: Oka Y