INSERM LNC UMR 1231, 21000 Dijon, France; University Bourgogne Franche-Comté, LNC UMR 1231, 21000 Dijon, France; LipSTIC LabEx, Fondation de Coopération Scientifique Bourgogne Franche-Comté, 21000 Dijon, France.
Department of Surgery, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, 62000 MD Maastricht, the Netherlands.
Cell Rep. 2017 Oct 31;21(5):1160-1168. doi: 10.1016/j.celrep.2017.10.008.
Glucagon-like peptide 1 (GLP-1) is a hormone released from enteroendocrine L cells. Although first described as a glucoregulatory incretin hormone, GLP-1 also suppresses inflammation and promotes mucosal integrity. Here, we demonstrate that plasma GLP-1 levels are rapidly increased by lipopolysaccharide (LPS) administration in mice via a Toll-like receptor 4 (TLR4)-dependent mechanism. Experimental manipulation of gut barrier integrity after dextran sodium sulfate treatment, or via ischemia/reperfusion experiments in mice, triggered a rapid rise in circulating GLP-1. This phenomenon was detected prior to measurable changes in inflammatory status and plasma cytokine and LPS levels. In human subjects, LPS administration also induced GLP-1 secretion. Furthermore, GLP-1 levels were rapidly increased following the induction of ischemia in the human intestine. These findings expand traditional concepts of enteroendocrine L cell biology to encompass the sensing of inflammatory stimuli and compromised mucosal integrity, linking glucagon-like peptide secretion to gut inflammation.
胰高血糖素样肽 1（GLP-1）是一种从肠内分泌 L 细胞释放的激素。尽管最初被描述为一种调节血糖的肠促胰岛素激素，但 GLP-1 还能抑制炎症并促进黏膜完整性。在这里，我们证明了脂多糖（LPS）通过 Toll 样受体 4（TLR4）依赖性机制在小鼠中迅速增加血浆 GLP-1 水平。葡聚糖硫酸钠处理后或通过小鼠缺血/再灌注实验对肠道屏障完整性进行实验操作，会引发循环 GLP-1 的快速上升。在炎症状态和血浆细胞因子和 LPS 水平发生可测量变化之前，就检测到了这种现象。在人类受试者中，给予 LPS 也会诱导 GLP-1 分泌。此外，在人类肠道发生缺血后，GLP-1 水平迅速升高。这些发现将肠内分泌 L 细胞生物学的传统概念扩展到包括炎症刺激和黏膜完整性受损的感知，将胰高血糖素样肽分泌与肠道炎症联系起来。
