Molecular mechanism of L-glutamate and GABA-mediated regulation of secretion of glucagon and insulin in islets of Langerhans

L-谷氨酸和GABA介导的胰岛胰高血糖素和胰岛素分泌调节的分子机制

• 批准号: 15390026
• 负责人: MORIYAMA Yoshinori
• 金额: $ 8.64万
• 依托单位: OKAYAMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-15390026/
• 关键词: B cell; A cell; islet of Langerhans; vesicular glutamate transporter; vesicular GABA transporter; glutamate; GABA; 小胞型グルタミン酸トランスポーター; 血糖; グルタミン酸トランスポーター

Vesicular glutamate transporter (VGLUT) and vesicular GABA transporter (VGAT) play essential roles in the glutamatergic and GABAergic chemical transduction, respectively. VGLUT and VGAT are present not only in the neuronal synaptic vesicles but also in the glucagon-containing secretory granules of A cells of islets of Langerhans, and are responsible for vesicular storage of glutamate and GABA, respectively. This research aimed to reveal the molecular mechanism of the glutamate- and GABA-mediated regulation of secretion of glucagon and insulin in the islets. During three years, we have obtained the following important results.(1)We have revealed topology of VGLUT2.(2)We have established an in vitro assay system for VGLUT, and identified some essential amino acid residues for transport of glutamate as well as targeting.(3)We have established an in vitro assay system for VGAT.(4)We have observed decreased glutamatergic signaling in VGLUT1 KO mice.(5)We have identified and characterized glutamate signaling pathway in intestinal L cells.(6)We have identified and characterized a series of receptors for regulation of secretion of insulin and glucagon.

囊泡谷氨酸转运体（VGLUT）和囊泡GABA转运体（VGAT）分别在谷氨酸能和GABA能的化学转导中起重要作用。VGLUT和VGAT不仅存在于神经元突触囊泡中，而且存在于胰岛A细胞的含胰高血糖素的分泌颗粒中，并且分别负责谷氨酸和GABA的囊泡储存。本研究旨在揭示谷氨酸和GABA介导的胰岛分泌胰高血糖素和胰岛素的分子机制。三年来，我们取得了以下重要成果。(1)We揭示了VGLUT 2的拓扑结构(2)We建立了VGLUT的体外检测体系，并鉴定了一些谷氨酸转运和靶向的必需氨基酸残基。(3)We建立了VGAT的体外检测体系。(4)We在VGLUT1 KO小鼠中观察到了降低的多巴胺能信号传导。(5)We已经确定并表征了肠L细胞中的谷氨酸信号通路。(6)We已经鉴定和表征了一系列用于调节胰岛素和胰高血糖素分泌的受体。

项目成果

小細胞型グルタミン酸トランスポーターの発見とグルタミン酸シグナリングの新展

小细胞谷氨酸转运蛋白的发现及谷氨酸信号传导的新进展

• 发表时间: 2003
• 期刊: 蛋白質核酸酵素 48(13)(short review)
• 作者: 高森茂雄;森山芳則
• 通讯作者: 森山芳則

Identification of essential amino acid residues of the NorM Na+/multidrug antiporter in Vibrio parahaemolyticus

• DOI: 10.1128/jb.187.5.1552-1558.2005
• 发表时间: 2005-03-01
• 期刊: JOURNAL OF BACTERIOLOGY
• 影响因子: 3.2
• 作者: Otsuka, M;Yasuda, M;Moriyama, Y
• 通讯作者: Moriyama, Y

Overexpression of constitutively activated glutamate dehydrogenase induces insulin secretion through enhanced glutamate oxidation

• DOI: 10.1152/ajpendo.00380.2003
• 发表时间: 2004-02-01
• 期刊: AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
• 影响因子: 5.1
• 作者: Anno, T;Uehara, S;Tanizawa, Y
• 通讯作者: Tanizawa, Y

Glutamatergic signaling in islet of Langerhans : A thread entangled.

朗格汉斯岛中的谷氨酸信号传导：一根纠缠的线。

• 发表时间: 2003
• 期刊: TRENDS in Pharmacological Sciences 24
• 作者: Moriyama;T.;Hayashi;M.
• 通讯作者: M.

高森 茂雄, 森山 芳則: "グルタミン酸化学伝達の鍵分子:小胞型グルタミン酸トランスポーター(special review)"細胞工学. 22(4). 441-447 (2003)

Shigeo Takamori、Yoshinori Moriyama：“谷氨酸氧化化学传递的关键分子：囊泡谷氨酸转运蛋白（特别评论）”细胞工程 22(4) (2003)。