Glutamate is a positive autocrine signal for glucagon release
Glutamate is a positive autocrine signal for glucagon release
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DOI：
10.1016/j.cmet.2008.03.004
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发表时间：
2008-06-01
期刊：
影响因子：
29
通讯作者：
Berggren, Per-Olof
中科院分区：
文献类型：
--
作者：
Cabrera, Over;Jacques-Silva, M. Caroline;Berggren, Per-Olof
葡萄糖稳态的一个重要特征是胰高血糖素从胰腺α细胞的有效释放。调节胰高血糖素分泌的分子机制仍然知之甚少。我们现在证明，人类α细胞表达离子型谷氨酸受体（iGluRs），这是胰高血糖素释放所必需的。葡萄糖浓度的降低导致谷氨酸从α细胞中释放。谷氨酸然后作用于iGluRs; AMPA/红藻氨酸盐型，导致膜去极化，电压门控Ca 2+通道开放，细胞质游离Ca 2+浓度增加，胰高血糖素释放增强。iGluR的体内阻断减少胰高血糖素分泌并加剧小鼠中胰岛素诱导的低血糖症。因此，谷氨酸自分泌反馈回路赋予α细胞有效增强其自身分泌活性的能力。这是保证充分胰高血糖素释放的先决条件，尽管在生理条件下血糖浓度变化相对适度。
An important feature of glucose homeostasis is the effective release of glucagon from the pancreatic alpha cell. The molecular mechanisms regulating glucagon secretion are still poorly understood. We now demonstrate that human a cells express ionotropic glutamate receptors (iGluRs) that are essential for glucagon release. A lowering in glucose concentration results in the release of glutamate from the alpha cell. Glutamate then acts on iGluRs; of the AMPA/kainate type, resulting in membrane depolarization, opening of voltage-gated Ca2+ channels, increase in cytoplasmic free Ca2+ concentration, and enhanced glucagon release. In vivo blockade of iGluRs reduces glucagon secretion and exacerbates insulin-induced hypoglycemia in mice. Hence, the glutamate autocrine feedback loop endows the alpha cell with the ability to effectively potentiate its own secretory activity. This is a prerequisite to guarantee adequate glucagon release despite relatively modest changes in blood glucose concentration under physiological conditions.