Glucagon-like peptide-1 potentiates glucose-stimulated insulin secretion via the transient receptor potential melastatin 2 channel
Glucagon-like peptide-1 potentiates glucose-stimulated insulin secretion via the transient receptor potential melastatin 2 channel
复制标题
胰高血糖素样肽-1 通过瞬时受体电位 melastatin 2 通道增强葡萄糖刺激的胰岛素分泌
DOI：
10.3892/etm.2017.5136
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发表时间：
2017-11-01
影响因子：
2.7
通讯作者：
Chen, Liming
中科院分区：
文献类型：
--
作者：
Pang, Bo;Kim, Sungjoon;Chen, Liming
瞬时受体电位melastatin 2（TRPM 2）通道是一种由cAMP激活的Ca 2+渗透性通道，在胰腺β细胞上表达，负责调节胰岛素分泌。众所周知，胰高血糖素样肽-1（GLP-1）可以增强葡萄糖刺激的胰岛素分泌（GSIS），并且细胞外葡萄糖浓度的变化会改变细胞内腺苷ATP和cAMP的水平。本研究假设TRPM 2介导GLP-1对胰岛素分泌的调节作用。结果表明，TRPM 2的沉默消除了GLP-1增强的胰岛素分泌，表明TRPM 2参与了这一过程。此外，在GLP-1和各种浓度的葡萄糖存在下，TRPM 2的电流记录和β细胞中所得胰岛素分泌的测量结果表明GLP-1通过TRPM 2通道调节GSIS。此外，抑制TRPM 2的活性或表达减弱GLP-1诱导的GSIS。通过使用特异性激活剂或抑制剂，本研究表明，GLP-1受体的两个主要下游效应物，由cAMP和蛋白激酶A直接激活的交换蛋白，差异影响GSIS和GLP-1增强的GSIS。总之，本研究揭示了TRPM 2在GLP-1调节的胰岛素分泌中的作用。本研究结果为糖尿病及其并发症的预防和治疗提供了新的途径。
The transient receptor potential melastatin 2 (TRPM2) channel, a Ca2+ permeable channel activated by cAMP, is expressed on pancreatic beta-cells and is responsible for the regulation of insulin secretion. It is known that glucose-stimulated insulin secretion (GSIS) can be potentiated by glucagon like peptide-1 (GLP-1), and that the changes in the extracellular glucose concentration alter the levels of intracellular adenosine ATP and cAMP. The present study hypothesized that TRPM2 mediates the modulatory effect of GLP-1 on insulin secretion. The results demonstrated that silencing of TRPM2 eliminated GLP-1-enhanced insulin secretion, indicating the involvement of TRPM2 in this process. In addition, the results of current recordings of TRPM2 and measurement of the resulting insulin secretion in beta-cells in the presence of GLP-1 and various concentrations of glucose suggest that GLP-1 regulates GSIS via the TRPM2 channel. Furthermore, inhibiting the activity or expression of TRPM2 attenuated GLP-1-induced GSIS. By using specific activators or inhibitors, the present study demonstrated that the two primary downstream effectors of the GLP-1 receptor, exchange protein directly activated by cAMP and protein kinase A, differentially influence GSIS and GLP-1-potentiated GSIS. In conclusion, the present study revealed the role of TRPM2 in GLP-1-regulated insulin secretion. The results of the present study provide a novel avenue for the prevention and treatment of diabetes and its complications.