D'Alessio David, Lu Wendell, Sun William, Zheng Shuqin, Yang Qing, Seeley Randy, Woods Stephen C, Tso Patrick
Department of Medicine, University of Cincinnati, Cincinnati, Ohio 45267, USA.
Am J Physiol Regul Integr Comp Physiol. 2007 Dec;293(6):R2163-9. doi: 10.1152/ajpregu.00911.2006. Epub 2007 Sep 26.
Glucagon like peptide 1 (GLP-1) is an intestinal hormone that plays an important role in glucose metabolism. GLP-1 is released from mucosal L cells following nutrient ingestion and contributes to the incretin effect, with the enhancement of insulin secretion occurring with enteral compared with intravenous glucose administration. The mechanisms linking nutrient absorption and GLP-1 secretion are unknown, and studies addressing this topic, particularly in small animal models, have been hampered by the relatively low concentrations of GLP-1 in the circulation. We hypothesized that GLP-1 levels would be higher in samples of intestinal lymph compared with plasma and could provide a novel system in which to study meal-induced hormone secretion. We addressed this hypothesis in conscious rats with indwelling catheters in the portal vein and distal intestinal lymph duct. These animals had plasma and lymph sampled before and for 240 min after instillation of a liquid meal in the gastrointestinal tract. Lymph contained detectable concentrations of glucose, insulin, and GLP-1 that were reliably measured using our assays. Before and after the Ensure feeding, plasma insulin levels were approximately two times as high in portal plasma as intestinal lymph. In marked contrast, GLP-1 levels were five to six times higher in lymph relative to portal plasma following nutrient administration. This relative difference in GLP-1 levels was even greater when lymph was compared with peripheral plasma and dramatically exceeded the ratio of lymph to plasma peptide tyrosine-tyrosine concentrations. This is the first observation of a gastrointestinal hormone being disproportionately transported in lymph. The remarkable levels of GLP-1 in intestinal lymph demonstrate the potential for lymphatic sampling as a more sensitive means of studying the secretory physiology of this hormone in vivo. In addition, these data raise the possibility that intestinal lymph may serve as a specialized signaling conduit for regulatory peptides secreted by gastrointestinal endocrine cells.
胰高血糖素样肽1（GLP-1）是一种在葡萄糖代谢中起重要作用的肠激素。营养物质摄入后，GLP-1从黏膜L细胞释放出来，有助于肠促胰岛素效应，与静脉注射葡萄糖相比，肠内给予葡萄糖时胰岛素分泌增强。营养物质吸收与GLP-1分泌之间的联系机制尚不清楚，针对这一主题的研究，尤其是在小动物模型中的研究，受到循环中GLP-1相对低浓度的阻碍。我们推测，与血浆相比，肠淋巴样本中的GLP-1水平会更高，并且可以提供一个新的系统来研究进餐诱导的激素分泌。我们在门静脉和远端肠淋巴管中留置导管的清醒大鼠中验证了这一假设。这些动物在胃肠道内注入流食之前和之后240分钟采集血浆和淋巴样本。淋巴中含有可检测浓度的葡萄糖、胰岛素和GLP-1，使用我们的检测方法可以可靠地进行测量。在给予安素喂养前后，门静脉血浆中的胰岛素水平大约是肠淋巴中的两倍。与之形成鲜明对比的是，营养物质给药后，淋巴中的GLP-1水平相对于门静脉血浆高出五到六倍。当将淋巴与外周血浆进行比较时，GLP-1水平的这种相对差异甚至更大，并且大大超过了淋巴与血浆中肽YY浓度的比值。这是首次观察到一种胃肠激素在淋巴中不成比例地运输。肠淋巴中GLP-1的显著水平表明，淋巴采样有可能作为一种更敏感的手段，用于在体内研究这种激素的分泌生理学。此外，这些数据还提出了一种可能性，即肠淋巴可能作为胃肠内分泌细胞分泌的调节肽的特殊信号传导途径。
