ABSTRACT
GLP-1 is a potent glucose-dependent insulinotropic hormone derived from intestinal L cells. Inflammatory Interleukin-27 (IL-27), a pleiotropic two-chain cytokine, is composed of EBI3 and IL-27 p28 subunits. IL-27 has a protective effect on pancreatic ß-cell function. The relationship between IL-27 and GLP-1 is still unexplored. Here we showed interleukin-27-stimulated GLP-1 production via the Stat3-mTOR-dependent mechanism. Interleukin 27 receptor subunit alpha (IL-27 Rα) was detected in ileum and STC-1 cells. Co-localization of EBI3 and GLP-1 was observed not only in mouse ileums but also in human ileums and colons. Third-ventricular infusion of IL-27 increased ileal and plasma GLP-1 in both lean C57BL/6J mice and diet-induced obese and diabetic mice. These changes were associated with a significant increase in Stat3-mTOR activity. Treatment of STC-1 cells with IL-27 contributed to the increments of Stat3-mTOR signaling and GLP-1. Interference of mTOR activity by mTOR siRNA or rapamycin abolished the stimulation of GLP-1 production induced by IL-27 in STC-1 cells. Stat3 siRNA also blocked the stimulus effect of IL-27 on GLP-1. IL-27 increased the interaction of mTOR and Stat3 in STC-1 cells. Our results identify Stat3-mTOR as a critical signaling pathway for the stimulation of GLP-1 induced by IL-27.
Subject(s)
Glucagon-Like Peptide 1/biosynthesis , Interleukin-27/metabolism , STAT3 Transcription Factor/metabolism , Signal Transduction , TOR Serine-Threonine Kinases/metabolism , Animals , Cell Line , Humans , Interferon-gamma/pharmacology , Interleukins/metabolism , Intestinal Mucosa/metabolism , Male , Mice, Inbred C57BL , Mice, Obese , Minor Histocompatibility Antigens/metabolism , Models, Biological , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptors, Interleukin/genetics , Receptors, Interleukin/metabolism , Sirolimus/pharmacologyABSTRACT
To establish a new identification method of Gypsum Fibrosum with FTIR and analyze different kinds of the sulfate mineral medicine with clustering method. With the use of FTIR, identify different kinds of sulfate mineral medicine, such as gypsum fibrosum, gypsum ustum and natrii sulfas , in addition, clustering method and first derivative spectra are used to analyze the intrinsic relationship in these kinds of sulfate mineral medicine. What's more, 24 batches of Gypsum Fibrosum samples which from different production are analyzed with FTIR; then the spectrum control fingerprint with pattern is established with common peaks; at last the similarity between the simple spectrum fingerprint and the spectrum control fingerprint is calculated with angle cosine value and correlation coefficient. There are distinctions about the wave number, the peak position, the spike and the peak intensity in the infrared spectroscopy and first derivative spectra. Therefore, the sulfate mineral medicine is divided into two main regions with the based on these clusters: put the gypsum fibrosum and gypsum ustum in the same class, the natrii sulfas in the other class. Between 400 and 4 000 cm-1, the experiment showed that 24 batches of samples were more than 0.980 0. Provide a new, rapid and specificity method for identification and standard of gypsum fibrosum and build a successful cluster analysis about the sulfate mineral medicine.
