PNAS：胰高血糖素通过自分泌信号调节自身合成

2012年12月4日讯 /生物谷BIOON/ --瑞典卡罗林斯卡医学眼的研究人员发现，生产胰高血糖素（glucagon）的细胞可被胰高血糖素自身刺激。该小组此前的一项研究表明，这一原则也适用于胰岛素。这意味着，机体中运行着一种反馈系统，从而激素分泌细胞可接收到一种即刻信号（immediate signal）来产生更多的激素。

相关研究结果已在线发表于《美国科学院院报》（PNAS）杂志上。

虽然胰岛素也是一种激素，但它能够降低血液中的葡萄糖水平，而胰高血糖素是一种增加血糖水平的激素。此前的研究表明，产生胰岛素的细胞能够被胰岛素本身激活。然而，是否这种过程只适用于胰岛素，抑或反映了一种普遍的生物学原理，仍然不清楚。现在，该团队已经证明，胰高血糖素也能刺激其自身的合成。

胰高血糖素结合至胰腺胰高血糖素分泌细胞的特定结合位点，随后影响了数个信号通路，导致产生胰高血糖素基因的激活。因此，分泌性激素影响自身的产生，这种正反馈过程（positive-feedback ），具有普遍的生物学意义。

“学习有关激素如何调节自身的生产，将最终使我们能够研究这一过程中的缺陷，如果这些缺陷与糖尿病有牵连，将使我们可能找到糖尿病拼图中的重要一块，”研究人员Per-Olof Berggren说道。

与胰高血糖素相关的拓展阅读：

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Glucagon regulates its own synthesis by autocrine signaling

Abstract:Peptide hormones are powerful regulators of various biological processes. To guarantee continuous availability and function, peptide hormone secretion must be tightly coupled to its biosynthesis. A simple but efficient way to provide such regulation is through an autocrine feedback mechanism in which the secreted hormone is “sensed” by its respective receptor and initiates synthesis at the level of transcription and/or translation. Such a secretion–biosynthesis coupling has been demonstrated for insulin; however, because of insulin’s unique role as the sole blood glucose-decreasing peptide hormone, this coupling is considered an exception rather than a more generally used mechanism. Here we provide evidence of a secretion–biosynthesis coupling for glucagon, one of several peptide hormones that increase blood glucose levels. We show that glucagon, secreted by the pancreatic α cell, up-regulates the expression of its own gene by signaling through the glucagon receptor, PKC, and PKA, supporting the more general applicability of an autocrine feedback mechanism in regulation of peptide hormone synthesis.