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研究生:游嵩勳
研究生(外文):Hsun-Hsin Yu
論文名稱:以高脂質誘發基因缺陷鼠來建立第二型糖尿病實驗動物模式暨探討山苦瓜合併螺旋藻改善胰島素耐受性之機制研究
論文名稱(外文):Study on the mechanism of bitter gourd combined with spirulina improved high fat diet-induced insulin dependent on genetically deficient TypeⅡ diabetic mice
指導教授:褚俊傑褚俊傑引用關係
指導教授(外文):Jiunn-Jye Chuu
學位類別:碩士
校院名稱:南台科技大學
系所名稱:生物科技系
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:2006
畢業學年度:94
語文別:中文
論文頁數:70
中文關鍵詞:第二型糖尿病山苦瓜螺旋藻
外文關鍵詞:TypeⅡ diabeticbitter gourdspirulina
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糖尿病是非常普遍的內分泌疾病,第一型及部分第二型糖尿病病人胰臟的β細胞質量隨著罹病時間而逐漸減少,以致胰島素分泌不足。其中百分之八十五的糖尿病病人是屬於非胰島素依賴型糖尿病(non-insulin-dependent diabetes meilitus, NIDDM)。目前的研究認為,糖尿病的主要特徵是胰島素分泌不正常及橫紋肌、肝臟對胰島素產生拮抗性。NIDDM的原因可能不是由於胰島素不足,而是胰島素未能有效發揮功能所致,這現象被稱為胰島素拮抗性(insulin resistance)。肌肉吸收葡萄糖的機轉主要是經胰島素敏感性的葡萄糖傳遞器-4 (GLUT-4) ,它的信號反應不良會造成胰島素對血漿葡萄糖濃度的反應減低。此外,insulin receptor substrate-1 (IRS-l)有可能是造成NlDDM的一個因子。與肥胖有關的因子,基本上PPAR-γ是屬於nuclear receptor superfamily, 經由基因之調節來控制脂肪之代謝及血管之發炎現象。
本研究主要利用diabetic KK/HIJ mice 模式,餵食高脂質飼料(high fed diet)來進一步誘發高與維持高血糖症狀。連續投予苦瓜萃取物,螺旋藻及苦瓜萃取物與螺旋藻(1:3)複合物于六週大non-insulin-dependent 小鼠共八週,分別於給藥前與投藥後每週分別測量血中blood glucose、triglyceride、cholesterol量。實驗中進行口服葡萄糖耐受性測試(OGTT)。為了探討是否type II 高血糖糖尿病鼠是否會造成末梢神經毒性, 我們運用電生理試驗來證明其神經肌肉傳導速度是否受影響。更進一步, 我們可透點西方點墨法(western blotting), 去檢查是否有與糖尿病特異性之蛋白如, GLUT-4, IRS-1 and PPAR-γ 的特殊表現 。最後, 透過SRB細胞毒性測試與流氏細胞儀我們可得到 pancreatic β cells 在不同抗糖尿病藥作用下, 是否會影響其程式性細胞死亡(apoptosis)的發生,以及在高濃度葡萄糖的作用下會不會降低凋亡情形發生,以期更進一步探討苦瓜萃取物改善胰島素耐受性 (insulin resistance)之藥理作用機制。
Type 2 diabetes mellitus (non-insulin-dependent diabetes meilitus, NIDDM) diabetes mellitus was expressed with increasing insulin resistance, eventually results in beta-cell dysfunction. Currently, the bitter gourd extract (Momordica charantia), spirulina and bitter gourd combined with spirulina has been studied for diabetes for lowering blood glucose levels in patients with diabetes mellitus and its complications (eg. nephropathy, cataract, insulin resistance). In order to elucidate the assessment of blood glucose, triglyceride, cholesterol and oral glucose/insulin tolerance after bitter gourd extract, spirulina and bitter gourd combined with spirulina oral administration at doses of 200 mg/kg/day for 8 weeks, this diabetic KK/HIJ mice model with high fed diet-induced hyperglycemia diabetes will be provided. Finally, the involvement of GLUT-4, IRS-1 and PPAR-γ expression on several metabolic organs of diabetic mice by western blotting will be manipulated.
Our preliminary data indicated that some induced-hyperglycemia KK-mice (over 150mg/dl, within fasting period) show abnormal triglyceride/cholesterol increase, glucose tolerance prolongation (OGTT) and decrease of GLUT-4 expression while the insulin maintained normal level by insulin ELISA test. To compare the similar type 2 diabetes KK-mice model, a part of STZ induced diabetes mice were grouped (blood glucose >100 and <200mg/dl) as type 2 diabetes mice model (normal insulin level), we found that the bitter gourd combined with spirulina also improve the glucose tolerance and reduce triglyceride/cholesterol level with increasing GLUT-4 , IRS-1 and PPAR-γ expression skeletal muscle,liver and adipocyte of high fat diet -induced diabetic mice by western blotting. Lately, the SRB assay and flow cytometry will claim the cytotoxicity and apoptotic index, respectively in pancreatic β cell line in vitro in a concentration-dependent manner.
中文摘要………………………………………………………………………………Ⅰ
英文摘要………………………………………………………………………………Ⅱ
目次……………………………………………………………………………………Ⅲ
圖目錄…………………………………………………………………………………Ⅴ
表目錄……………………………………………………………………………Ⅷ
縮寫對照表…………………………………………………………………………Ⅸ

第一章 研究動機……………………………………………………………………1
第二章 文獻探討……………………………………………………………………3
2.1 糖尿病簡介……………………………………………………………………3
2.1.1 糖尿病的定義..………………………………………………………3
2.1.2 糖尿病的分類…………………………………………………………3
2.1.3 糖尿病的病因…………………………………………………………5
2.1.4 糖尿病診斷……………………………………………………………7
2.1.5 糖尿病流行病學………………………………………………………7
2.2 胰島素訊息傳遞與作用……………………………………………………8
2.2.1 胰島素受體……………………………………………………………9
2.2.2 胰島素受體基質……………………………………………………11
2.2.3 葡萄糖轉運蛋白-4…………………………………………………11
2.2.4 PPARs…………………………………………………………………12
2.3 保健食品之中草藥概述…………………………………………………13
2.3.1 山苦瓜…………………………………………………………………13
2.3.2 螺旋藻…………………………………………………………………14
第三章 材料與方法……………………………………………….……18
3.1 糖尿病實驗動物模式之建立……………………………………………18
3.1.1 誘發糖尿病動物模式之建立……………………………………18
3.1.2 第一型與第二型糖尿病實驗動物與試驗……………………19
第四章 結果………………………………………………………………………26
4.1 STZ-induced DM model………………………………………………26
4.2 KK/HIJ DM model………………………………………………26
4.3 西方墨點法western blotting………………………………………27
4.4 高劑量葡萄糖誘發胰臟β細胞之毒性測試…………………………28
4.5 流氏細胞儀之測定(FACS)………………………………………………29
4.6 電生理…………………………………………………………………………29
第五章 討論…………………………………………………………………………30
第六章 結論…………………………………………………………………………34
第七章 結果圖表…………………………………………………………………37
第八章 參考文獻……………………………………………………………………68
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陳紀樺 2004. PPAR γ與糖尿病. 食品工業. 第36卷 第六期:18-30
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