https://scholars.lib.ntu.edu.tw/handle/123456789/495879
標題: | The hepatic protection effects of hepassocin in hyperglycemic crisis | 作者: | Ou H.-Y. Wu H.-T. Lin C.-H. Du Y.-F. Hu C.-Y. Hung H.-C. Wu P. HUNG-YUAN LI SHU-HUEI WANG Chang C.-J. |
公開日期: | 2017 | 出版社: | Endocrine Society | 卷: | 102 | 期: | 7 | 起(迄)頁: | 2407-2415 | 來源出版物: | Journal of Clinical Endocrinology and Metabolism | 摘要: | Context: High glucose generates reactive oxygen species (ROS) and contributes to glucotoxicity in hepatocytes, and hyperglycemia causes structural and functional damage to the liver. However, only a mild hepatic dysfunction was observed in subjects with hyperglycemic crisis, implying a factor exists to exert a hepatic protective effect. Hepassocin is a hepatokine that modulates the proliferation and metabolism of hepatocytes and also exerts protective activity in liver injury. However, its role in hyperglycemic crisis-induced hepatic dysfunction remains unknown. Objective: To investigate the possible hepatic protection effects of hepassocin in hyperglycemic crisis. Design, Setting, and Patients: Plasma hepassocin concentrations and routine biochemistry were measured in 21 patients with hyperglycemic crisis before and after standard treatments. The effects of hepassocin on hepatic functions were evaluated in streptozotocin-induced hyperglycemic mice (STZ mice). HepG2 cells were used to clarify the possible mechanisms regulating hepassocin expression. Results: Plasma hepassocin concentrations decreased significantly in subjects with hyperglycemic crisis after standard treatment accompanied by improved hepatic functions. Correction of hyperglycemia in STZ mice also decreased the hepatic hepassocin expression. Injection of recombinant hepassocin improved hepatic functions and histologic changes and increased the expression of antioxidative stress proteins, including superoxide dismutase 1 (SOD1). In HepG2 cells, high glucose increased hepassocin expression through signal transducer and activator of transcription 3 and hepatocyte nuclear factor-related pathways. We also demonstrated that hepassocin increased SOD1 expression through an extracellular signal-regulated kinase 1/2 nuclear factor erythroid-2-related factor 2 pathway, decreasing ethyl acetate-induced ROS production and improving cell viability. Conclusions: Increased hepassocin secretion in hyperglycemic crisis might offset the deleterious effects of hyperglycemia on hepatocytes. Copyright ? 2017 Endocrine Society. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85023183190&doi=10.1210%2fjc.2016-3287&partnerID=40&md5=86b8a8356ea8be02570b22bf482df67a https://scholars.lib.ntu.edu.tw/handle/123456789/495879 |
ISSN: | 0021-972X | DOI: | 10.1210/jc.2016-3287 | SDG/關鍵字: | copper zinc superoxide dismutase; hepassocin; hepatocyte nuclear factor; membrane protein; mitogen activated protein kinase 1; mitogen activated protein kinase 3; STAT3 protein; transcription factor Nrf2; unclassified drug; antidiabetic agent; FGL1 protein, human; reactive oxygen metabolite; small interfering RNA; streptozocin; tumor protein; adult; animal experiment; animal model; animal tissue; Article; cell metabolism; cell proliferation; cell viability; clinical article; controlled study; enzyme phosphorylation; female; human; human cell; hyperglycemia; liver injury; liver protection; male; middle aged; mouse; nonhuman; priority journal; protein blood level; protein expression; protein function; protein secretion; analysis of variance; animal; C57BL mouse; cell culture; disease model; epidemiology; genetic transfection; Hep-G2 cell line; hyperglycemia; liver failure; metabolism; mouse mutant; procedures; randomization; real time polymerase chain reaction; Western blotting; Adult; Analysis of Variance; Animals; Blotting, Western; Cells, Cultured; Disease Models, Animal; Hep G2 Cells; Humans; Hyperglycemia; Hypoglycemic Agents; Liver Failure; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Middle Aged; Neoplasm Proteins; Random Allocation; Reactive Oxygen Species; Real-Time Polymerase Chain Reaction; RNA, Small Interfering; Sampling Studies; Streptozocin; Transfection |
顯示於: | 醫學系 |
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