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研究生:李天瑞
研究生(外文):Tien-Jui Lee
論文名稱:數種食材萃物對脂肪或肌肉細胞葡萄糖攝取之影響
論文名稱(外文):The Effects of Several Food Extracts on Glucose Uptake in 3T3-L1 Adipocytes and C2C12 Myotubes
指導教授:黃青真黃青真引用關係
指導教授(外文):Ching-Jang Huang
學位類別:碩士
校院名稱:國立臺灣大學
系所名稱:微生物與生化學研究所
學門:生命科學學門
學類:微生物學類
論文種類:學術論文
論文出版年:2008
畢業學年度:97
語文別:中文
論文頁數:111
中文關鍵詞:胰島素抗性苦瓜山藥脂肪細胞肌肉細胞葡萄糖
外文關鍵詞:insulin resistancebitter gourdyamadipocytemyotubeglucose
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現今罹患代謝症候群的人口日益增加,有鑑於藥物治療所難以避免的副作用,傳統中草藥或食材的替代療法與其有效成分漸受重視。山藥與苦瓜長久以來被視為具有降血糖、改善糖尿病的食材,且於許多動物與人體試驗中獲得證實,但對於其中有效成分及作用機制卻不完全明瞭。因此本研究以C2C12肌肉細胞與3T3-L1脂肪細胞株的葡萄糖攝取模式,在正常無胰島素抗性的情況與以1 mM棕櫚酸誘發胰島素抗性下,探討山藥乙酸乙酯萃物與苦瓜乙酸乙酯萃物與其中不皂化物、乙醇萃物、水萃物是否有改善胰島素抗性的效果。結果發現山藥乙酸乙酯萃物對正常肌肉細胞具有類似胰島素效應,對於基礎與胰島素刺激下葡萄糖攝取均有促進效果,但對脂肪細胞則無促進效果。而苦瓜不皂化物可增進脂肪細胞葡萄糖攝取,但對胰島素抗性無改善。苦瓜以水萃物最有潛力,12小時處理下對於正常或有胰島素抗性的脂肪細胞,皆可隨劑量增進其葡萄糖攝取,卻會受熱破壞此一活性。此效果不會被compound c抑制,也無法完全被wortmannin所抑制,並不造成AMPK或Akt磷酸化增加。且苦瓜水萃物對長時間高胰島素所誘發的胰島素抗性沒有改善效果。而不同於先前研究的結果,發現3kDa以下小分子亦含有活性成分,顯示整體苦瓜水萃物改善胰島素抗性效應於低濃度時來自非蛋白質部分。針對於苦瓜水萃物發現的活性物質與其作用機制途徑值得進一步探討,具有改善胰島素抗性潛力。
Metabolic syndrome and insulin resistance have become worldwide epidemiological issues. Dietary supplement and traditional medicines may be a natural source of for the development of the treatment to counteract insulin resistance in stead of those widely used agents with many side effects. Yam and bitter gourd are common vegetable and tonic foods in Asian and have been shown to exert hypoglycemic effects in animal models and humans, but the mechanism and active constituents are not totally understood. Here we measured 3H-labeled 2-deoxyglucose uptake by normal and pamitate-induced insulin resistance 3T3-L1 adipocytes and C2C12 myotubes, and evaluated whether various extracts from yam and bitter gourd could improve. It is found that yam EA extract showed an insulin-like pattern in myotubes but not in adipocytes. Bitter gourd water extract is the most active fraction that showed a promotion of glucose uptake in both normal or insulin resistant 3T3-L1 adipocytes in a dose-dependent manner. This activity is diminished by heating the extract at 100℃ for 10 min. The activity was not inhibited by compound c but was partially inhibited by wortmannin. Neither AMPK phosphorylation nor Akt activation was changed. Interestingly, the water extract of bitter gourd could not improve the insulin resistance that induced by chronic insulin treatment. It has also been found that constituents with a MW less than 3 kDa were also active. The precise structure in bitter gourd water extract and mechanism of action of those active molecules are worth to be further examined. Bitter gourd thus has the potential for ameliorating insulin resistance.
口試委員會審定書 …………………………………………………… I
謝誌 …………………………………………………………………… II
中文摘要 ……………………………………………………………… IV
英文摘要 ……………………………………………………………… VI

第一章 緒論 ……………………………………………………… 1
第一節 研究動機與目的 ………………………………………… 1
第二節 文獻回顧 ………………………………………………… 2
一、 代謝症候群 ……………………………………………… 2
(一) 代謝症候群的定義 ……………………………………… 2
(二) 我國代謝症候群的現狀 ………………………………… 2
二、 胰島素抗性 ……………………………………………… 4
(一) 胰島素 …………………………………………………… 4
(二) 胰島素促進葡萄糖攝取的訊息傳遞路徑 ……………… 5
(三) 葡萄糖轉運子 …………………………………………… 7
(四) AMPK (AMP-activating protein kinase) pathway … 8
(五) 肌肉組織與胰島素抗性 ………………………………… 10
(六) 脂肪組織與胰島素抗性 ………………………………… 10
(七) 發炎反應 ………………………………………………… 13
三、 過氧化體增生劑活化受器 ……………………………… 15
(一) PPAR種類與作用機制 …………………………………… 15
(二) PPAR與胰島素抗性 ……………………………………… 15
四、 食材樣品 ………………………………………………… 17
(一) 山藥 ……………………………………………………… 17
(二) 苦瓜 ……………………………………………………… 17
第三節 實驗假說與架構設計 …………………………………… 24

第二章 數種食材萃物對脂肪細胞葡萄糖攝取之影響 ………… 27
第一節 前言 ……………………………………………………… 27
第二節 材料與方法 ……………………………………………… 28
一、 細胞株 …………………………………………………… 28
二、 培養基與藥品試劑 ……………………………………… 28
三、 儀器設備 ………………………………………………… 29
四、 實驗材料 ………………………………………………… 30
五、 實驗方法 ………………………………………………… 31
六、 數據整理與統計分析 …………………………………… 33
第三節 結果 ……………………………………………………… 35
一、 細胞模式之建立 ………………………………………… 35
二、 山藥乙酸乙酯萃物對已分化3T3-L1脂肪細胞葡萄糖
攝取之影響 ……………………………………………… 35
三、 2381山苦瓜乙酸乙酯萃物對已分化3T3-L1脂肪細胞
葡萄糖攝取之影響 ……………………………………… 36
四、 2381山苦瓜不皂化物對已分化3T3-L1脂肪細胞葡萄
糖攝取之影響 …………………………………………… 36
五、 2381山苦瓜水萃物對已分化3T3-L1脂肪細胞葡萄糖
攝取之影響 ……………………………………………… 37
六、 CK山苦瓜乙醇萃物對已分化3T3-L1脂肪細胞葡萄糖
攝取之影響 ……………………………………………… 37
七、 白苦瓜水萃物對已分化3T3-L1脂肪細胞葡萄糖攝取
之影響 …………………………………………………… 38
第四節 討論 ……………………………………………………… 47
第五節 結論 ……………………………………………………… 50

第三章 白苦瓜水萃物增進脂肪細胞葡萄糖攝取之探討 ……… 51
第一節 前言 ……………………………………………………… 51
第二節 材料與方法 ……………………………………………… 52
一、 細胞株 …………………………………………………… 52
二、 培養基與藥品試劑 ……………………………………… 52
三、 儀器設備 ………………………………………………… 55
四、 實驗材料 ………………………………………………… 56
五、 實驗方法 ………………………………………………… 56
六、 數據整理與統計分析 …………………………………… 58
第三節 結果 ……………………………………………………… 59
一、 白苦瓜水萃物無法改善高胰島素處理引起脂肪細胞
之胰島素抗性 …………………………………………… 59
二、 白苦瓜水萃物加熱後減弱對脂肪細胞胰島素抗性的
改善功效 ………………………………………………… 59
三、 白苦瓜水萃物改善脂肪細胞胰島素抗性能力與胰島
素訊息傳遞路徑有關 …………………………………… 59
四、 白苦瓜水萃物改善脂肪細胞胰島素抗性能力並非透
過AMPK途徑 ……………………………………………… 60
五、 白苦瓜水萃物小於3 kDa成分參與了部分改善胰島素
抗性的角色 ……………………………………………… 60
第四節 討論 ……………………………………………………… 69
第五節 結論 ……………………………………………………… 72

第四章 數種食材萃物對肌肉細胞葡萄糖攝取之影響 ………… 73
第一節 前言 ……………………………………………………… 73
第二節 材料與方法 ……………………………………………… 74
一、 細胞株 …………………………………………………… 74
二、 培養基與藥品試劑 ……………………………………… 74
三、 儀器設備 ………………………………………………… 74
四、 實驗材料 ………………………………………………… 74
五、 實驗方法 ………………………………………………… 75
六、 數據整理與統計分析 …………………………………… 76
第三節 結果 ……………………………………………………… 77
一、 細胞模式之建立 ………………………………………… 77
二、 山藥乙酸乙酯萃物對已分化C2C12肌肉細胞株葡萄糖
攝取之影響 ……………………………………………… 77
三、 白苦瓜水萃物對已分化C2C12肌肉細胞株葡萄糖攝取
之影響 …………………………………………………… 78
第四節 討論 ……………………………………………………… 83
第五節 結論 ……………………………………………………… 86

第五章 綜合討論與總結論 ……………………………………… 87
第一節 綜合討論 ………………………………………………… 87
第二節 總結論 …………………………………………………… 92

第六章 參考文獻 ………………………………………………… 93
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