TRP Channels of Islets
TRP Channels of Islets
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DOI：
10.1007/978-94-007-0265-3_42
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发表时间：
2011-01-01
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影响因子：
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通讯作者：
Islam, Md Shahidul
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作者：
Islam, Md Shahidul
在正常人体中，胰腺β细胞大部分时间处于就绪模式而不是关闭模式。当处于就绪模式时，正常的β细胞可以很容易地被各种明显微不足道的刺激所激活。在READY模式中，β细胞由于其高输入电阻而高度可兴奋。由各种化学和物理刺激触发的各种阳离子通道介导的各种小的去极化电流可以使细胞活化。属于瞬时受体电位（TRP）家族的几种多模态离子通道可能介导将β细胞从READY模式转换为ON模式所需的去极化电流。由于TRP通道，我们现在知道Sturgess等人在1986年（FEBS Lett 208：397-400）描述的Ca 2+激活的单价阳离子选择性通道是TRPM 4，而Herson和阿什福德在1997年（J Physiol 501：59-66）描述的H2 O2激活的非选择性阳离子通道是TRPM 2。葡萄糖代谢产生热量，热量似乎是由温度敏感的TRP通道（如TRPM 2通道）感知的第二信使。TRPM 5通道的整体敲除损害小鼠的胰岛素分泌可能参与β细胞功能调节的其他TRP包括TRPC 1、TRPC 4、TRPM 3、TRPV 2和TRPV 4。未来的研究需要加强，以研究胰岛TRP通道的分子调节，并在人类胰岛衰竭的发病机制中阐明它们在调节人类β细胞功能中的作用。
In the normal human body pancreatic beta-cells spend most of the time in a READY mode rather than in an OFF mode. When in the READY mode, normal beta-cells can be easily SWITCHED ON by a variety of apparently trivial stimuli. In the READY mode beta-cells are highly excitable because of their high input resistance. A variety of small depolarizing currents mediated through a variety of cation channels triggered by a variety of chemical and physical stimuli can SWITCH ON the cells. Several polymodal ion channels belonging to the transient receptor potential (TRP) family may mediate the depolarizing currents necessary to shift the beta-cells from the READY mode to the ON mode. Thanks to the TRP channels, we now know that the Ca2+-activated monovalent cation selective channel described by Sturgess et al. in 1986 (FEBS Lett 208:397-400) is TRPM4, and that the H2O2-activate non-selective cation channel described by Herson and Ashford, in 1997 (J Physiol 501:59-66) is TRPM2. Glucose metabolism generates heat which appears to be a second messenger sensed by the temperature-sensitive TRP channels like the TRPM2 channel. Global knock-out of TRPM5 channel impairs insulin secretion in mice. Other TRPs that may be involved in the regulation of beta-cell function include TRPC1, TRPC4, TRPM3, TRPV2 and TRPV4. Future research needs to be intensified to study the molecular regulation of the TRP channels of islets, and to elucidate their roles in the regulation of human beta-cell function, in the context of pathogenesis of human islet failure.