Physiological significance of thermosensitive TRPM2 channel

温敏TRPM2通道的生理意义

• 批准号: 19209006
• 负责人: TOMINAGA Makoto
• 金额: $ 31.62万
• 依托单位: National Institutes of Natural Sciences Okazaki Research Facilities
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-19209006/
• 关键词: TRPM2チャネル; 免疫機能; インスリン分泌; 膵臓; 神経科学; 生理学; 温度

Transient receptor potential melastatin 2 (TRPM2) is a non-selective Ca^<2+>-permeable cation channel, and is known to be activated by adenosine 5'-diphosphoribose (ADP-ribose) and hydrogen peroxide. 1) Upon screening of the compounds, it was clarified that 2-aminoethoxydiphenyl borate (2-APB) exhibited the rapid and reversible inhibition of TRPM2 channels and that 2-APB inhibited heat-evoked insulin release from the pancreatic islets. 2) To clarify the involvement of TRPM2 in insulin secretion, we analyzed TRPM2 knock-out (TRPM2-KO) mice, and found that TRPM2 is involved in insulin secretion stimulated by glucose and that further potentiated by incretins, suggesting that TRPM2 may be a new target for diabetes therapy. 3) To determine the effects of a small reduction in ambient temperature on energy metabolism, we compared two groups of mice ; one exposed to a cool environment (20℃) and the other maintained in a near-thermoneutral environment (25℃) for 10 days. We found that a small reduction in ambient temperature can affect glucose homeostasis through regulation of insulin secretion and preferentially enhances fat storage in IWAT.

瞬时受体电位melastatin 2（TRPM 2）是一种非选择性的Ca^2+-可渗透的阳离子通道，并且已知被腺苷5 '-二磷酸核糖（ADP-核糖）和过氧化氢激活。1)在筛选化合物时，阐明了2-氨基乙氧基二苯基硼酸酯（2-APB）对TRPM 2通道表现出快速和可逆的抑制作用，2-APB抑制了胰岛的热诱发胰岛素释放。2)为了阐明TRPM 2在胰岛素分泌中的作用，我们分析了TRPM 2基因敲除（TRPM 2-KO）小鼠，发现TRPM 2参与葡萄糖刺激的胰岛素分泌，并被肠促胰岛素进一步增强，这表明TRPM 2可能是糖尿病治疗的新靶点。3)为了确定环境温度小幅降低对能量代谢的影响，我们比较了两组小鼠;一组暴露于凉爽环境（20℃），另一组保持在近热中性环境（25℃）中10天。我们发现，环境温度的小幅降低可以通过调节胰岛素分泌来影响葡萄糖稳态，并优先增强IWAT中的脂肪储存。

项目成果

Contribution of TRPV1 to the bradykinin-evoked nociceptive behavior and excitation of cutaneous sensory neurons

• DOI: 10.1016/j.neures.2008.08.004
• 发表时间: 2008-11-01
• 期刊: NEUROSCIENCE RESEARCH
• 影响因子: 2.9
• 作者: Katanosaka, Kimiaki;Banik, Ratan Kumar;Mizumura, Kazue
• 通讯作者: Mizumura, Kazue

TRPM2 is a key player for insulin secretion

TRPM2 是胰岛素分泌的关键角色

• 发表时间: 2010
• 作者: Uchida K;Dezaki K;Damdindorj B;Mori Y;Minokoshi Y;Yada T;Tominaga M
• 通讯作者: Tominaga M

Lack of TRPM2 impaired insulin secretion and glucose metabolisms in mice.

• DOI: 10.2337/db10-0276
• 发表时间: 2011-01
• 期刊: Diabetes
• 影响因子: 7.7
• 作者: Uchida K;Dezaki K;Damdindorj B;Inada H;Shiuchi T;Mori Y;Yada T;Minokoshi Y;Tominaga M
• 通讯作者: Tominaga M

Inhibition of TRPM2 channels by 2-APB

2-APB 对 TRPM2 通道的抑制

• 发表时间: 2008
• 期刊: Br.J.Pharmacol 153-(6)
• 作者: Togashi K;Inada H;Tominaga M.
• 通讯作者: Tominaga M.

Intracellular alkalization causes pain sensation through activation of TRPA1.

细胞内碱化通过激活 TRPA1 引起痛觉。

• 发表时间: 2008
• 期刊: J. Clon. Invest 118
• 作者: Fujita F;Uchida K;Moriyama T;Shima A;Shibasaki K;Inada H;Sokabe T;Tominaga M.
• 通讯作者: Tominaga M.