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系統識別號 U0026-0812200914271376
論文名稱(中文) 尿囊素改善糖尿病作用之研究
論文名稱(英文) Investigation of the antidiabetic action of allantoin
校院名稱 成功大學
系所名稱(中) 藥理學研究所
系所名稱(英) Department of Pharmacology
學年度 96
學期 2
出版年 97
研究生(中文) 溫雅如
研究生(英文) Ya-ju Wen
電子信箱 s2695102@mail.ncku.edu.tw
學號 s2695102
學位類別 碩士
語文別 中文
論文頁數 86頁
口試委員 口試委員-徐鳳麟
指導教授-鄭瑞棠
口試委員-劉怡旻
中文關鍵字 咪唑啉接受體  糖尿病  尿囊素 
英文關鍵字 diabetes  imidazoline receptor  allantoin 
學科別分類
中文摘要 過去研究顯示,活化咪唑啉接受體具有調降血糖的作用。本研究旨欲探討尿囊素 (Allantoin),一種由天然植物紫草 (Symphytum officinale)萃取所得之咪唑啉 (imidazoline)結構類似物,是否能透過活化咪唑啉接受體進而改善血糖恆定。結果發現,於正常大白鼠及streptozotocin誘導之第一型糖尿病大白鼠投予尿囊素後,皆可觀察到降血糖的作用,然而,正常大白鼠的血中胰島素濃度在給藥後並無明顯變化,此結果指出尿囊素可能透過非胰島素依賴的機制而調降血糖。另外,投予尿囊素可改善正常大白鼠的葡萄糖耐受性及增加離體骨骼肌對葡萄糖的攝取能力。而此二者的作用皆會被前處理第二型咪唑啉接受體 (I2R)拮抗劑BU224所阻斷。過去研究發現,活化I2R可提升第一型糖尿病大鼠血中腦內啡濃度,並透過嗎啡μ型受體的活化進而產生降血糖作用。實驗發現,尿囊素能提升第一型糖尿病大鼠血中腦內啡濃度進而降低血糖,而此作用可受到BU224及naloxonazine的阻斷。許多研究顯示,活化腺苷單磷酸活化蛋白激酶(AMP-activated protein kinase, AMPK),可刺激第四型葡萄糖運輸蛋白 (glucose transporter type 4, Glut4)的轉位及蛋白表現,進而增加骨骼肌細胞對葡萄糖的攝取能力。實驗也發現,尿囊素可增加AMPK的磷酸化程度及Glut4的表現,進而促進小鼠肌纖維母細胞對葡萄糖的攝取能力,而上述作用皆可被BU224、AMPK抑制劑 (Compound C)及I2AR拮抗劑 (amiloride)所阻斷。此外,藉由胰島素耐受性試驗、葡萄糖耐受性試驗及Homeostasis Model Assessment的檢測,發現尿囊素可改善第一型糖尿病大鼠對胰島素的敏感性及第二型糖尿病大鼠的胰島素阻抗現象。綜合以上實驗,本研究發現尿囊素主要藉由活化I2R而具有改善葡萄糖代謝平衡的作用,並針對I2R的降糖機轉有更深入的瞭解。
英文摘要 Previous studies have been demonstrated that activation of imidazoline receptor exerted a hypoglycemic effect. The present study is to investigate whether allantoin, an imidazoline derivative extracted from Symphytum officinale, acted on imidazoline receptor to improve glucose homeostasis. Results showed hypoglycemic effects were observed in Wistar rats and streptozotocin-induced type 1 diabetic rat (STZ-induced diabetic rats) after allantoin treatment. However, allantoin did not alter plasma insulin levels in Wistar rats, indicating that this effect of allantoin may be through an insulin-independent mechanism. In addition, allantoin improved glucose tolerance and increased glucose uptake in isolated skeletal muscle in Wistar rats. Both effects of allantoin were blocked by pretreatment of BU224, an I2R antagonist. Previous studies have been shown that activation of I2R increased the plasma β-endorphin level, which exerted a function to decrease plasma glucose through opioid-μreceptor in STZ-induced diabetic rats. We found that allantoin elevated β-endorphin levels to decrease plasma glucose, which was blocked by BU224 and nalonxonazine. Several studies have shown that activation of AMP-activated protein kinase (AMPK) stimulated translocation and protein expression of glucose transporter type 4 (Glut4) to increase glucose uptake in skeletal muscle cells. We found that allantoin increased AMPK phosphorylation and Glut4 expression to raise glucose uptake in C2C12 mouse myoblast cells, and these effects could be blocked by BU224, AMPK inhitor (Compound C), and I2AR antagonist (amiloride). Furthermore, we also observed that allantoin improves insulin sensitivity in STZ-induced diabetic rats and ameliorate insulin resistance in fructose-induced type 2 diabetic rats by insulin tolerance test, glucose tolerance test and Homeostasis Model Assessment. Taken together, we found that allantoin have a beneficial effect on glucose homeostasis through I2R, and further clarify the possible mechanisms of I2R for the hypoglycemia.
論文目次 中文摘要 …………………………………………………………Ⅰ
英文摘要 …………………………………………………………Ⅳ
縮寫表 ……………………………………………………………1
第一章 緒論 ……………………………………………………4
第二章 實驗材料與方法 ………………………………………10
第三章 實驗結果 ………………………………………………30
第四章 討論 ……………………………………………………42
第五章 結論 ……………………………………………………50
參考文獻 …………………………………………………………52
附圖 ………………………………………………………………60
自述 ………………………………………………………………86
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