A novel variant of ionotropic glutamate receptor regulates somatostatin secretion from δ-cells of islets of Langerhans
A novel variant of ionotropic glutamate receptor regulates somatostatin secretion from δ-cells of islets of Langerhans
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DOI：
10.2337/diabetes.53.7.1743
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发表时间：
2004-07-01
期刊：
影响因子：
7.7
通讯作者：
Moriyama, Y
中科院分区：
文献类型：
--
作者：
Muroyama, A;Uehara, S;Moriyama, Y
许多代谢因素影响胰岛β细胞分泌胰岛素和α细胞分泌胰高血糖素以调节血糖。来自δ细胞的生长抑素被认为是胰岛功能的局部抑制剂，通过激活胰岛细胞中的生长抑素受体来减少胰岛素和胰高血糖素的分泌。高葡萄糖通过葡萄糖代谢增加来自δ细胞的生长抑素分泌，其方式与来自β细胞的胰岛素分泌相似。然而，低葡萄糖如何触发生长抑素分泌尚不清楚。由于L-谷氨酸在低葡萄糖条件下与α细胞的胰高血糖素共同分泌，并作为主要的细胞间信使，我们假设谷氨酸信号触发生长抑素的分泌。在这项研究中，我们发现，δ细胞表达GluR 4c-flip，一个新发现的GluR 4的剪接变体，（RS）-α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）型离子型谷氨酸受体的大鼠。用L-谷氨酸、AMPA或红藻氨酸处理后，在低葡萄糖条件下显著刺激分离的胰岛分泌生长抑素。谷氨酸依赖的生长抑素分泌是Ca ~（2+）依赖的，并被6-氰基-7-硝基喹喔啉-2，3-二酮阻断。生长抑素反过来又抑制α-细胞分泌L-谷氨酸和胰高血糖素。这些结果表明，在低葡萄糖条件下，L-谷氨酸通过GluR 4c翻转受体触发δ细胞的生长抑素分泌。释放的生长抑素可完成对α细胞的反馈抑制。因此，α-和δ-细胞可以通过L-谷氨酸和生长抑素信号传导彼此通信。
Many metabolic factors affect the secretion of insulin from beta-cells and glucagon from alpha-cells of the islets of Langerhans to regulate blood glucose. Somatostatin from delta-cells, considered a local inhibitor of islet function, reduces insulin and glucagon secretion by activating somatostatin receptors in islet cells. Somatostatin secretion from delta-cells is increased by high glucose via glucose metabolism in a similar way to insulin secretion from beta-cells. However, it is unknown how low glucose triggers somatostatin secretion. Because L-glutamate is cosecreted with glucagon from alpha-cells under low-glucose conditions and acts as a primary intercellular messenger, we hypothesized that glutamate signaling triggers the secretion of somatostatin. In this study, we showed that delta-cells express GluR4c-flip, a newly identified splicing variant of GluR4, an (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type ionotropic glutamate receptor of rat. After treatment with L-glutamate, AMPA, or kainate, secretion of somatostatin from isolated islets was significantly stimulated under low-glucose conditions. The glutamate-dependent somatostatin secretion was Ca2+ dependent and blocked by 6-cyano-7-nitroquinoxaline-2,3-dione. Somatostatin in turn inhibited the secretion Of L-glutamate and glucagon from a-cells. These results indicate that L-glutamate triggers somatostatin secretion from delta-cells by way of the GluR4c-flip receptor under low-glucose conditions. The released somatostatin may complete the feedback inhibition of alpha-cells. Thus, alpha- and delta-cells may communicate with each other through L-glutamate and somatostatin signaling.