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研究生:陳雅妍
研究生(外文):Ya-Yen Chen
論文名稱:不同昇糖指數之根莖主食類對於高血糖及胰島素阻抗大白鼠其體內胰島素敏感性及胰島素訊息傳遞路徑之影響
論文名稱(外文):Effects of the Starchy Foods with Different Glycemic Index on the Insulin Sensitivity and Insulin Signaling in the Hyperglycemic and Insulin-Resistant Rats
指導教授:劉珍芳劉珍芳引用關係
口試委員:趙蓓敏盧義發葉松鈴謝榮鴻
口試日期:2013-06-05
學位類別:博士
校院名稱:臺北醫學大學
系所名稱:保健營養學研究所
學門:醫藥衛生學門
學類:營養學類
論文種類:學術論文
論文出版年:2013
畢業學年度:101
語文別:中文
論文頁數:129
中文關鍵詞:昇糖指數胰島素敏感性胰島素訊息傳遞發炎
外文關鍵詞:glycemic indexinsulin sensitivityinsulin signalinginflammation
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本論文之目的有二:第一為測定臺灣幾種常見水果及根莖主食類的昇糖指數值 (glycemic index, GI),第二個目的是以不同GI值的根莖主食類作為食材,並分別以高血糖及胰島素阻抗之大白鼠作為動物模式,探討不同GI值的根莖主食類對於大白鼠體內胰島素訊息傳遞路徑及胰島素敏感性之影響。第一部份:測定臺灣幾種常見水果及根莖主食類之GI值,實驗食材的水果類包括: 水梨、芭樂、香蕉、黃金奇異果、葡萄、荔枝、富士蘋果、木瓜、鳳梨、芒果及龍眼;根莖主食類則包括地瓜、馬鈴薯、玉米、蓮藕、芋頭及皇帝豆六種。結果顯示,水梨、蘋果、地瓜及蓮藕GI值較低;芋頭為中GI;龍眼、芒果、玉米及馬鈴薯GI值較高。從中挑選高GI的馬鈴薯及低GI的地瓜作為動物實驗的飼料介入食材。第二部份:本研究利用Sprague-Dawley (SD)鼠,以腹腔注射streptozotocin (STZ)/ nicotinamide以誘導大鼠產生高血糖,之後餵食含地瓜粉或馬鈴薯粉的飲食四週。在實驗前後各進行一次IPGTT (intraperitoneal glucose tolerance test) 實驗,四週後犧牲大鼠取其血液及骨骼肌進行胰島素訊息傳遞路徑相關蛋白質之分析。第三部份:先餵食SD大鼠高果糖飲食將之誘導成為胰島素阻抗的狀態,之後餵食含地瓜粉或馬鈴薯粉的飲食四週。四週後在胰島素的刺激下犧牲大鼠,取其血液及骨骼肌進行adipokines, 發炎性激素及胰島素訊息傳遞路徑相關蛋白質之分析。綜合以上兩部分研究結果顯示,在動物實驗中發現餵食含地瓜粉之飲食四週後,高血糖大鼠之血糖曲線下面積顯著下降,顯示其葡萄糖耐受性及餐後血糖反應已被改善。此外,餵食含地瓜粉之飲食的大鼠其骨骼中IRS-1及GLUT4之蛋白質表現量顯著上升。在胰島素阻抗的動物模式中,發現餵食含地瓜粉之飲食四週後,大鼠之血糖及胰島素曲線下面積、胰島素阻抗指標值 (HOMA-IR) 顯著下降,血液中發炎性指標 (包括TNF-α, resistin, RBP-4, IL-6) 的濃度也顯著下降。在胰島素的刺激下,發現餵食含地瓜粉之飲食的大鼠其骨骼中phospho-Tyr-IRS-1的表現量及細胞膜上GLUT4的表現量顯著上升。結論:餵食含地瓜粉之飲食四週後,可改善高血糖及胰島素阻抗大白鼠之餐後血糖反應及胰島素敏感性,並推測其機制可能與胰島素訊息傳遞路徑的正面調控及發炎現象的改善有關。
PURPOSES: This study was to measure the GIs of several kinds of fruits and starchy foods and evaluate the effects of low GI starchy foods on the insulin signaling and insulin sensitivity in the hyperglycemic and insulin-resistant rats. METHODS: This study was divided into three parts. Part 1 study: Measure the GIs of several common kinds of fruits and starchy foods in Taiwan, including pear, Fuji apple, papaya, guava, banana, pineapple, golden kiwifruit, grape, litchi, mango, longan, sweet potato, potato, corn, lotus root, taro and lima bean. Results showed that pear, apple, sweet potato and lotus root belong to low GI; taro belongs to median GI; longan, mango, corn and potato belong to high GI. We choose sweet potato and potato to be the sources of low- and high- GI starch. Part 2 study: Hyperglycemia was induced by using STZ/nicotinamide in Sprague-Dawley (SD) rats and then fed a diet containing 575 g/kg as either sweet potato starch or potato starch for 4 weeks. We did two IPGTTs before the start and 2 days before the end of the experimental period to observe the postprandial glycemic response. After 4 weeks, blood and the skeletal muscle was collected to measure the protein expression of insulin receptor (IR), insulin receptor substract-1 (IRS-1) and glucose transporter 4 (GLUT4). Part 3 study: SD rats were feed with high-fructose diet for 6 weeks to induce insulin resistance. Then the rats were fed with a diet containing 575 g/kg as either sweet potato starch or potato starch for 4 weeks. After 4 weeks, blood and the skeletal muscle was collected under the stimulation of insulin. Blood was used to measure the levels of adipocytokines and proinflammatory cytokines; the skeletal muscle was used to measure the protein expression of phosphorylayted-insulin receptor (IR), phosphorylayted-insulin receptor substract-1 (IRS-1) and glucose transporter 4 (GLUT4). RESULTS: From part 2 study, we found that the area under curve (AUC) for blood glucose at 4th week in the sweet potato starch-fed group were significant lower than those at 0th week. This result showed that compared to the potato starch-fed group, lower-GI sweet potato starch improved the postprandial glycemic response in hyperglycemic rats. The lower-GI sweet potato starch feeding for 4 weeks upregulated the protein expression of IRS-1 and GLUT4 in the skeletal muscle of hyperglycemic rats. From part 3 study, results showed that hyperinsulinemia and insulin sensitivity was improved in low-GI starch-fed rats. The concentration of TNF-alpha, IL-6, resistin and RBP-4 (retinol binding protein-4) were significantly lower in low-GI starch-fed rats. This suggested the proinflammatory status was improved in low-GI starch-fed rats. Low-GI starch feeding for 4 weeks significantly enhanced the protein expression of phospho-Tyr-IRS-1 and improved the translocation of GLUT4 to the plasma membrane in the skeletal muscle. CONCLUSION: Our results showed low-GI starch feeding for 4 weeks could improve the postprandial glycemic response and insulin sensitivity in hyperglycemic and insulin-resistant rats and may via the ameliorating of the adipocytokines, proinflammatory status and insulin signaling.
目錄
中文摘要I
英文摘要III
縮寫對照表VI
目錄VII
表目錄 X
圖目錄 XI
第一章 緒論 1
第二章 文獻回顧 3
第一節 第2型糖尿病 3
一、第2型糖尿病的盛行率及其併發症 3
二、胰島素阻抗 4
三、第2型糖尿病的飲食控制 6
四、Streptozotocin (STZ) 誘導高血糖鼠之動物模式 7
五、高果糖飲食所誘導之胰島素阻抗動物模式10
第二節 昇糖指數 12
一、昇糖指數的定義與生理意義 12
二、昇糖指數相關研究 13
三、葡萄糖毒性14
四、富含醣類的食物 16
第三節 alpha-glucosidase inhibitor 對血糖控制的重要性 18
第四節 胰島素之訊息傳遞 (Insulin Signaling) 20
一、胰島素及其受器 20
二、胰島素之訊息傳遞 24
第三章 研究動機 26
第四章 臺灣常見水果及根莖主食類的GI值及alpha-glucosidase抑制活性測定 29
第一節 臺灣常見水果及根莖主食類的GI值測定 29
一、受試者招募與受測食材 29
二、實驗流程 31
第二節 臺灣常見水果及根莖主食類的 alpha-glucosidase抑制活性測定 33
一、水果類前處理 33
二、根莖主食類前處理 33
三、alpha-glucosidase抑制活性測定 34
第三節 實驗結果 35
第四節 討論 37
一、水果及根莖主食類之 GI值及 alpha-glucosidase 之抑制活性 37
二、動物實驗介入食材之選擇 38
三、地瓜與馬鈴薯 GI值不同之可能因素 39
第五章 不同GI值的根莖主食類對於以STZ/nicotinamide誘導的高血糖大白鼠其體內胰島素訊息傳遞路徑的影響 42
第一節 高血糖大白鼠動物模式的誘導及其飼料配製 42
第二節 分析項目 46
一、血糖及胰島素濃度 46
二、血脂質之測定 47
三、大鼠骨骼肌中insulin receptor (IR, 包括磷酸化形式), insulin receptor substrate-1 (IRS-1, 包括磷酸化形式) 及 glucose transporter 4 (GLUT4) 之蛋白質表現量測定 47
四、統計分析 51
第三節 結果 52
一、大鼠之體重變化及餵食效率 52
二、大鼠之血液生化值 52
三、IPGTT實驗中之血糖曲線下面積 55
四、大鼠骨骼肌中胰島素訊息傳遞路徑相關蛋白質之蛋白質表現量 59
第四節 討論 65
一、低GI飲食對於高血糖大鼠葡萄糖耐受性及餐後血糖反應的調控 65
二、低GI飲食對於高血糖大鼠胰島素敏感性的影響 66
三、低GI飲食對於胰島素訊息傳遞路徑的影響 68
四、實驗限制 69
第五節 結論 70
第六章 不同GI值的根莖主食類對於以高果糖飲食所誘導之胰島素阻抗大白鼠其體內胰島素敏感性的影響 71
第一節 胰島素阻抗大白鼠之誘導 71
第二節分析項目 76
一、血糖及胰島素濃度 76
二、血脂質之測定 76
三、血漿中脂肪細胞激素及發炎性激素濃度測定 77
四、大鼠骨骼肌中胰島素訊息傳遞路徑相關之蛋白質表現量測定 80
五、統計分析 83
第三節 結果 84
一、大鼠之體重變化及餵食效率 84
二、大鼠之血液生化值 84
三、IPGTT實驗中之血糖及胰島素曲線下面積 87
四、大鼠血液中adipokines及proinflammatory cytokines之濃度 91
五、大鼠骨骼肌中胰島素訊息傳遞相關蛋白質之蛋白質表現量 93
第四節 討論 99
一、6週高果糖飲食對於大鼠生理狀況的影響 99
二、低GI飲食對胰島素敏感性的影響及其機制探討 100
三、實驗限制 104
第五節 結論 106
第七章 總結 107
第八章 未來應用與展望 108
第九章 參考文獻 109
第十章 附錄與發表論文清單 129













表目錄
表一 受測水果類及根莖主食類之品種 30
表二 臺灣常見水果及根莖主食類之GI值及alpha-glucosidase抑制活性 36
表三 動物飼料之組成 (以AIN-93為基礎) 45
表四 大鼠在餵食實驗飼料四週後之體重、餵食效率及器官重量 53
表五 大鼠在餵食實驗飼料四週後之血液生化值 54
表六 第0週及餵食4週後大鼠在IPGTT中之血糖曲線下面積 56
表七 經6週高果糖飲食誘導後大鼠之空腹血糖、胰島素及HOMA-IR值 73
表八 大鼠在餵食實驗飼料四週後之體重、餵食效率及器官重量 85
表九 大鼠在餵食實驗飼料四週後之血液生化值 86
表十 餵食實驗飼料四週後大鼠在IPGTT中之血糖及胰島素曲線下面積 88
表十一 大鼠在餵食實驗飼料四週後血液中之脂肪細胞激素及發炎激素濃度 92












圖目錄
圖一 STZ的化學結構 8
圖二 STZ誘發大鼠胰臟β-cell毒性之機制 9
圖三 人體胰島素之序列結構 21
圖四 胰島素受器的構造 23
圖五 胰島素訊息傳遞路徑 25
圖六 台農57號地瓜41
圖七 克尼伯種馬鈴薯41
圖八 餵食含馬鈴薯粉之飲食的高血糖大鼠四週後在IPGTT實驗中之血糖曲線57
圖九 餵食含地瓜粉之飲食的高血糖大鼠四週後在IPGTT實驗中之血糖曲線58
圖十 大鼠骨骼肌中胰島素受器的蛋白質表現量60
圖十一 大鼠骨骼肌中磷酸化形式胰島素受器的蛋白質表現量61
圖十二 大鼠骨骼肌中胰島素受器受質-1的蛋白質表現量 62
圖十三 大鼠骨骼肌中磷酸化形式胰島素受器受質-1的蛋白質表現量63
圖十四 大鼠骨骼肌中葡萄糖轉運體第4型的蛋白質表現量 64
圖十五 胰島素阻抗大鼠餵食四週後在IPGTT實驗中之血糖曲線 89
圖十六 胰島素阻抗大鼠餵食四週後在IPGTT實驗中之胰島素曲線 90
圖十七 大鼠骨骼肌中胰島素受器的蛋白質表現量 94
圖十八 大鼠骨骼肌中磷酸化形式胰島素受器的蛋白質表現量 95
圖十九 大鼠骨骼肌中胰島素受器受質-1的蛋白質表現量96
圖二十 大鼠骨骼肌中磷酸化形式胰島素受器受質-1的蛋白質表現量 97
圖二十一 大鼠骨骼肌細胞膜中葡萄糖轉運體第4型的蛋白質表現量 98
中文部分
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