Department of Clinical Sciences and Education, Södersjukhuset, Karolinska Institutet, SE-118 83 Stockholm, Sweden.
Adv Exp Med Biol. 2011;704:811-30. doi: 10.1007/978-94-007-0265-3_42.
In the normal human body pancreatic β-cells spend most of the time in a READY mode rather than in an OFF mode. When in the READY mode, normal β-cells can be easily SWITCHED ON by a variety of apparently trivial stimuli. In the READY mode β-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 β-cells from the READY mode to the ON mode. Thanks to the TRP channels, we now know that the Ca(2+)-activated monovalent cation selective channel described by Sturgess et al. in 1986 (FEBS Lett 208:397-400) is TRPM4, and that the H(2)O(2)-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 β-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 β-cell function, in the context of pathogenesis of human islet failure.
在正常人体中，胰岛β细胞大部分时间处于准备状态（READY mode），而不是关闭状态（OFF mode）。当处于准备状态时，正常β细胞很容易被各种看似微不足道的刺激激活。在准备状态下，β细胞由于其高输入电阻而具有高度兴奋性。通过各种阳离子通道介导的各种小去极化电流，由各种化学和物理刺激触发，可以激活细胞。几种属于瞬时受体电位（TRP）家族的多模态离子通道可能介导将β细胞从准备状态切换到激活状态（ON mode）所需的去极化电流。由于 TRP 通道，我们现在知道，1986 年 Sturgess 等人描述的 Ca(2+)激活的单价阳离子选择性通道（FEBS Lett 208:397-400）是 TRPM4，而 Herson 和 Ashford 于 1997 年描述的 H(2)O(2)激活的非选择性阳离子通道（J Physiol 501:59-66）是 TRPM2。葡萄糖代谢产生热量，这似乎是热敏 TRP 通道（如 TRPM2 通道）感知的第二信使。TRPM5 通道的全局敲除会损害小鼠的胰岛素分泌。其他可能参与β细胞功能调节的 TRP 包括 TRPC1、TRPC4、TRPM3、TRPV2 和 TRPV4。未来的研究需要加强，以研究胰岛 TRP 通道的分子调节，并阐明它们在人类β细胞功能调节中的作用，以阐明人类胰岛衰竭发病机制中的作用。
