Role of crosstalk between peripheral circadian clock and NO-cGMP system of pancreatic beta-cells in the pathogenesis of diabetes

外周生物钟与胰腺β细胞NO-cGMP系统之间的串扰在糖尿病发病机制中的作用

• 批准号: 23590192
• 负责人: ISHIKAWA Tomohisa
• 金额: $ 3.33万
• 依托单位: University of Shizuoka
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23590192/
• 关键词: 糖尿病; シグナル伝達; 薬学

This study was aimed to investigate the relation between the regulation of NO-cGMP system by the endogenous NO synthase inhibitor ADMA and peripheral circadian clock in pancreatic beta-cells and the involvement of these systems in the pathogenesis of diabetes. We found that the expression of the ADMA metabolic enzyme DDAH2 in beta-cells is suppressed by high glucose, suggesting that the NO-cGMP system is down-regulated by the accumulation of ADMA in diabetes. Unfortunately, we could not obtain any evidence for a relation between the NO-cGMP system and peripheral circadian clock in beta-cells. On the other hand, melatonin, a circadian synchronizer, was suggested to inhibit insulin secretion from beta-cells in the presence of GLP-1 secreted from the gastrointestinal mucosa in response to a meal. Thus, the possibility is raised that some relation between food intake and circadian rhythm exists in the regulation of beta-cell functions.

本研究旨在探讨内源性NO合成酶抑制剂ADMA对胰腺β细胞NO-cGMP系统的调节与外周生物钟的关系及其在糖尿病发病机制中的作用。我们发现β细胞中ADMA代谢酶DDAH 2的表达受到高糖的抑制，这表明NO-cGMP系统在糖尿病中被ADMA的积累下调。不幸的是，我们无法获得任何证据表明β细胞中NO-cGMP系统与外周生物钟之间的关系。另一方面，建议褪黑激素（昼夜节律同步器）在响应于进餐而从胃肠道粘膜分泌的GLP-1的存在下抑制β细胞的胰岛素分泌。因此，提出了在β细胞功能的调节中存在食物摄入和昼夜节律之间的某种关系的可能性。

项目成果

皮膚血管におけるα1受容体を介した収縮機構の違い

α1受体介导的皮肤血管收缩机制的差异

• 发表时间: 2014
• 作者: 石田裕丈;菱沼瑛多;北川智章;斉藤真也;石川智久
• 通讯作者: 石川智久

カフェインはマウス肝星細胞の活性化を抑制する

咖啡因抑制小鼠肝星状细胞的活化

• 发表时间: 2011
• 作者: Murayama;N.;van Beuningen;R.;Suemizu;H.;Guguen-Guillouzo;C.;Shibata;N.;Yajima;K.;Utoh;M.;Shimizu;M.;Chesne;C.;Nakamura;M.;Guengerich;F. P.;Houtman;R.;and Yamazaki;H;齊藤真也
• 通讯作者: 齊藤真也

Structure-dependent effects of green tea catechins on insulin secretion from INS-1 cells

绿茶儿茶素对 INS-1 细胞胰岛素分泌的结构依赖性影响

• 发表时间: 2012
• 作者: Yukiko Kaneko;Miki Takii;Yumiko Kojima;Hiroko Yokosawa;and Tomohisa Ishikawa
• 通讯作者: and Tomohisa Ishikawa

Calcitonin ameliorates enhanced arterial contractility after chronic constriction injury of the sciatic nerve in rats.

降钙素可改善大鼠坐骨神经慢性收缩损伤后增强的动脉收缩力。

• 发表时间: 2011
• 期刊: Fundam.Clin.Pharmacol.
• 作者: Kashiwagi K.;Terui Y.;Higashi K.;Okudaira H.;Ochiai E.;Tomitori H.;Nishimura K.;Yamamoto K.;Ishihama A.;Igarashi K.;岡野登志夫;船越英資;Takeshi Yoshimura
• 通讯作者: Takeshi Yoshimura

Depression of Type I Diacylglycerol Kinases in Pancreatic β-Cells From Male Mice Results in Impaired Insulin Secretion

• DOI: 10.1210/en.2013-1356
• 发表时间: 2013-11-01
• 期刊: ENDOCRINOLOGY
• 影响因子: 4.8
• 作者: Kaneko, Yukiko Kurohane;Kobayashi, Yosuke;Ishikawa, Tomohisa
• 通讯作者: Ishikawa, Tomohisa