GLP-1, the gut-brain, and brain-periphery axes.
GLP-1, the gut-brain, and brain-periphery axes.
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DOI：
10.1900/rds.2011.8.418
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发表时间：
2011-01-01
期刊：
影响因子：
--
通讯作者：
Burcelin, Remy
中科院分区：
文献类型：
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作者：
Cabou, Cendrine;Burcelin, Remy
胰高血糖素样肽1 （Glucagon-like peptide 1, GLP-1）是一种肠道激素，直接与位于胰腺β细胞表面的GLP-1受体结合，增强葡萄糖诱导的胰岛素分泌。除了胰腺作用外，GLP-1还可以通过与其在肠道和大脑神经细胞上表达的受体相互作用来诱导代谢行为。GLP-1也可以被认为是一种由脑干神经元细胞合成的神经肽，并将其直接释放到下丘脑。在这种环境下，GLP-1被认为控制许多代谢和心血管功能，如胰岛素分泌、葡萄糖的产生和利用以及动脉血流。然而，这两个位置在调节葡萄糖稳态中的确切作用尚不清楚。在这篇综述中，我们重点介绍了支持肠-脑和脑外周轴在葡萄糖稳态控制中的作用的最新实验数据。我们还关注肠道GLP-1靶向β细胞和脑细胞对葡萄糖稳态调节的相关性。除了它对β细胞的作用外，我们发现了解GLP-1的生理作用将有助于开发基于GLP-1的治疗方法，通过直接触发肠脑轴或大脑来控制2型糖尿病的血糖。GLP-1的这种多效性作用是一个重要的概念，它可能有助于解释在治疗过程中，2型糖尿病患者可以被识别为“应答者”和“无应答者”。
Glucagon-like peptide 1 (GLP-1) is a gut hormone which directly binds to the GLP-1 receptor located at the surface of the pancreatic beta-cells to enhance glucose-induced insulin secretion. In addition to its pancreatic effects, GLP-1 can induce metabolic actions by interacting with its receptors expressed on nerve cells in the gut and the brain. GLP-1 can also be considered as a neuropeptide synthesized by neuronal cells in the brain stem that release the peptide directly into the hypothalamus. In this environment, GLP-1 is assumed to control numerous metabolic and cardiovascular functions such as insulin secretion, glucose production and utilization, and arterial blood flow. However, the exact roles of these two locations in the regulation of glucose homeostasis are not well understood. In this review, we highlight the latest experimental data supporting the role of the gut-brain and brain-periphery axes in the control of glucose homeostasis. We also focus our attention on the relevance of beta-cell and brain cell targeting by gut GLP-1 for the regulation of glucose homeostasis. In addition to its action on beta-cells, we find that understanding the physiological role of GLP-1 will help to develop GLP-1-based therapies to control glycemia in type 2 diabetes by triggering the gut-brain axis or the brain directly. This pleiotropic action of GLP-1 is an important concept that may help to explain the observation that, during their treatment, type 2 diabetic patients can be identified as 'responders' and 'non-responders'.