https://scholars.lib.ntu.edu.tw/handle/123456789/563781
標題: | The role of phosphoinositide 3-kinase/Akt signaling in low-dose mercury-induced mouse pancreatic β-cell dysfunction in vitro and in vivo | 作者: | Ya W.C. Chun F.H. KEH-SUNG TSAI RONG-SEN YANG Cheng C.Y. Ching Y.Y. Shoei Y.L.-S. SHING-HWA LIU |
公開日期: | 2006 | 卷: | 55 | 期: | 6 | 起(迄)頁: | 1614-1624 | 來源出版物: | Diabetes | 摘要: | The relationship between oxidation stress and phosphoinositide 3-kinase (PI3K) signaling in pancreatic β-cell dysfunction remains unclear. Mercury is a well-known toxic metal that induces oxidative stress. Submicromolar- concentration HgCl2 or methylmercury triggered reactive oxygen species (ROS) production and decreased insulin secretion in β-cell-derived HIT-T15 cells and isolated mouse islets. Mercury increased PI3K activity and its downstream effector Akt phosphorylation. Antioxidant N-acetyl-L-cysteine (NAC) prevented mercury-induced insulin secretion inhibition and Akt phosphorylation but not increased PI3K activity. Inhibition of PI3K/Akt activity with PI3K inhibitor or by expressing the dominant-negative p85 or Akt prevented mercury-induced insulin secretion inhibition but not ROS production. These results indicate that both PI3K and ROS independently regulated Akt signaling-related, mercury-induced insulin secretion inhibition. We next observed that 2- or 4-week oral exposure to low-dose mercury to mice significantly caused the decrease in plasma insulin and displayed the elevation of blood glucose and plasma lipid peroxidation and glucose intolerance. Akt phosphorylation was shown in islets isolated from mercury-exposed mice. NAC effectively antagonized mercury-induced responses. Mercury-induced in vivo effects and increased blood mercury were reversed after mercury exposure was terminated. These results demonstrate that low-dose mercury-induced oxidative stress and PI3K activation cause Akt signaling-related pancreatic β-cell dysfunction. ? 2006 by the American Diabetes Association. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-33748311969&doi=10.2337%2fdb06-0029&partnerID=40&md5=f77d66426425442dc267113d2f2e0e7c https://scholars.lib.ntu.edu.tw/handle/123456789/563781 |
ISSN: | 0012-1797 | DOI: | 10.2337/db06-0029 | SDG/關鍵字: | acetylcysteine; glucose; mercury; methylmercury; phosphatidylinositol 3 kinase; protein kinase B; reactive oxygen metabolite; animal cell; animal experiment; animal model; antioxidant activity; article; cell culture; cell function; controlled study; diabetes mellitus; enzyme activity; enzyme inhibition; experimental model; glucose blood level; glucose tolerance test; in vitro study; in vivo study; insulin release; male; mouse; nonhuman; oxidative stress; pancreas disease; pancreas islet beta cell; peroxidation; priority journal; protein phosphorylation; signal transduction; Western blotting; 1-Phosphatidylinositol 3-Kinase; Acetylcysteine; Animals; Blood Glucose; Blotting, Western; Cell Line, Tumor; Cell Survival; Chromones; Cricetinae; Dose-Response Relationship, Drug; Free Radical Scavengers; Glucose Tolerance Test; Insulin; Insulin-Secreting Cells; Islets of Langerhans; Lipid Peroxidation; Male; Mercury; Mercury Compounds; Mice; Mice, Inbred ICR; Morpholines; Phosphorylation; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; Signal Transduction |
顯示於: | 醫學系 |
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