代谢组学分析流程及常用软件：CellMetab美学者发表肝脏氨基酸代谢研究论文
代谢组学分析流程及常用软件：CellMetab美学者发表肝脏氨基酸代谢研究论文Decreasing glucagon action lowers the blood glucose and may be useful therapeutically for diabetes. However interrupted glucagon signaling leads to α cell proliferation. To identify postulated hepatic-derived circulating factor(s) responsible for α cell proliferation we used transcriptomics/proteomics/metabolomics in three models of interrupted glucagon signaling and found that proliferation of
2017年6月6日，国际著名学术杂志《Cell》子刊《Cell metabolism》杂志在线发表了美国范德堡大学医学中心Alvin C. Powers教授、Wenbiao Chen教授和厦门大学药学院李明玉副教授合作的一篇研究论文。论文题为“Interrupted Glucagon Signaling Reveals Hepatic α Cell Axis and Role for L-Glutamine in α Cell Proliferation”。Alvin C. Powers教授课题组博士后E. Danielle Dean为论文第一作者，李明玉副教授为第二作者。
论文以小鼠、斑马鱼为模型，并结合人胰岛α细胞为研究对象，运用转录组学、蛋白质组学及代谢组学等手段。揭示了α细胞增生过程中，肝脏中的氨基酸代谢引起变化，并促使血液循环中的游离氨基酸显著提高，其中的增加的L-谷氨酰胺是促进α细胞增生的主要因子之一。该论文解决了长期以来该领域的一个疑团即α细胞增生的驱动分子，为以胰高血糖素受体(GCGR)为靶点的糖尿病治疗手段，以及诱导增生α细胞转化成胰岛β细胞的糖尿病治疗手段提供了理论基础。
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原文摘要：
Decreasing glucagon action lowers the blood glucose and may be useful therapeutically for diabetes. However interrupted glucagon signaling leads to α cell proliferation. To identify postulated hepatic-derived circulating factor(s) responsible for α cell proliferation we used transcriptomics/proteomics/metabolomics in three models of interrupted glucagon signaling and found that proliferation of mouse zebrafish and human α cells was mTOR and FoxP transcription factor dependent. Changes in hepatic amino acid (AA) catabolism gene expression predicted the observed increase in circulating AAs. Mimicking these AA levels stimulated α cell proliferation in a newly developed in vitro assay with L-glutamine being a critical AA. α cell expression of the AA transporter Slc38a5 was markedly increased in mice with interrupted glucagon signaling and played a role in α cell proliferation. These results indicate a hepatic α islet cell axis wher glucagon regulates serum AA availability and AAs especially L-glutamine regulate α cell proliferation and mass via mTOR-dependent nutrient sensing.
