Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/13548
標題: 鉻對胰島素訊息傳遞及肝損傷之研究
The study of chromium on insulin signaling and liver injury
作者: 陳文英
Chen, Wen-Ying
關鍵字: chromium

insulin resistance
oxidative stress
liver injury
胰島素阻抗
氧化傷害
肝損傷
出版社: 獸醫學系暨研究所
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摘要: 微量元素鉻具有抗氧化之能力,且可改善胰島素阻抗,常用於輔助第2型糖尿病之控制。胰島素阻抗及氧化傷害是導致代謝症候群及慢性肝病之主要原因,然而,鉻在其中所扮演的分子調控機制仍不清楚。本研究論文透過基因缺陷胰島素抗性小鼠及總膽管結紮誘發膽汁鬱積肝纖維化大鼠模式來探討三價鉻影響胰島素阻抗、氧化傷害及肝纖維化的分子作用機制。於肥胖KK/HlJ糖尿病小鼠之研究發現,每日補充鉻可有效增加骨骼肌中胰島素受體訊息傳遞相關蛋白之表現,如IRS1、PI3-K、葡萄糖運送蛋白4 (glucose transporter 4),同時可刺激Akt的活性、抑制JNK活性、降低IRS1 ubiquitinization及IRS1-Ser 307的磷酸化,補充鉻亦可有效減低血液及肌肉中前發炎因子的表現。利用總膽管結紮誘發慢性膽汁鬱積動物模式顯示,補充鉻可有效減輕膽管結紮鼠之肝傷害及降低肝中脂質過氧化物丙二醛(氧化傷害指標)之含量,而此抗氧化作用伴隨著增加肝中抗氧化酵素Cu/Zn-SOD、Mn-SOD、CAT和GPx的活性及增加肝中抗氧化酵素Cu/Zn-SOD和CAT的蛋白表現。綜合上述糖尿病及膽汁鬱積動物模式研究結果得知,鉻對代謝相關慢性病之胰島素阻抗、氧化傷害及肝纖維化具有改善作用。
Chromium is well known for its effects on improving insulin resistance and has been used as an alternative remedy for type 2 diabetes. In addition, some experimental and clinical studies have shown the antioxidative potential of chromium. Insulin resistance and oxidative stress are principal causative factors in the development of metabolic syndrome and chronic liver disease. However, the detailed molecular mechanisms on insulin signaling and the effect on chronic liver disease are not completely characterized. In this study, the potential contribution of trivalent chromium in the events of insulin resistance, oxidative stress and liver fibrosis were investigated via genetically inherited insulin resistant KK/H1J diabetic mice and bile duct ligation (BDL)-induced cholestasis-related liver fibrotic rats. In obese KK/HlJ diabetic mice, it was shown that chromium supplementation activated post-receptor insulin signaling such as increasing insulin receptor substrate 1 (IRS1), IRS1 tyrosine phosphorylation, p85α regulatory subunit of phosphatidylinositol 3-kinase and glucose transporter 4 expression, stimulating Akt activity, down-regulating c-Jun N-terminal kinase (JNK) activity, and decreasing IRS1 ubiquitinization and insulin resistance-associated IRS1 phosphorylation (IRS1-Ser307) in skeletal muscle. In addition, chromium supplementation attenuated pro-inflammatory cytokine expression in both blood circulation and skeletal muscle. In a rat model of chronic cholestasis induced BDL, chromium supplementation demonstrated significantly lower hepatic damage and the level of lipid peroxidation product malondialdehyde (MDA), an index of oxidative stress, in BDL rats. The antioxidative effect of chromium was accompanied by enhancing in hepatic Cu/Zn-superoxide dismutase (SOD), Mn-SOD, catalase (CAT), and glutathione peroxidase (GPx) activities, and hepatic Cu/Zn-SOD and catalase protein expression. Taken together, the results of the diabetic and cholestasis animal studies, it is concluded that chromium provide beneficial effects against insulin resistance, oxidative stress, and liver fibrosis.
URI: http://hdl.handle.net/11455/13548
其他識別: U0005-1303200912475500
文章連結: http://www.airitilibrary.com/Publication/alDetailedMesh1?DocID=U0005-1303200912475500
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