本研究利用 streptozotocin 及 nicotinamide 誘導雄性 Sprague-Dawley 大白鼠為第 2 型糖尿病，並在高膽固醇飲食下，給予 7% 幾丁聚醣及 0.5% 維生素 C 達 20 週，觀察其醣類及脂質代謝之變化。實驗共分為四組：正常組 (normal control, N)、糖尿病控制組 (diabetes control, D)、糖尿病添加 7% 幾丁聚醣組 (diabetes + 7% chitosan, D7C) 及糖尿病添加 7% 幾丁聚醣和 0.5% 維生素 C 組 (diabetes + 7% chitosan + 0.5% sodium ascorbate, D7CA)。結果發現，實驗 4 週後，D7C 及 D7CA 能顯著降低第 2 型糖尿病大白鼠禁食血漿總膽固醇，於實驗 9 及 16 週後之口服葡萄糖耐受性試驗中 (oral glucose tolerance test, OGTT)，D7C 能顯著降低 OGTT 30、60 及 120 分鐘血糖值，D7CA 於實驗第 16 週能顯著降低 OGTT 60 分鐘血糖值。實驗進行至 20 週，D7C 及 D7CA 對於其血糖及血總膽固醇皆無影響，且 D7C 會顯著增加第 2 型糖尿病大白鼠血三酸甘油酯及血漿低密度脂蛋白膽固醇 (very low density lipoprotein cholesterol) 含量，且脂肪組織脂蛋白脂解酶 (lipoprotein lipase) 活性較低，D7CA 提高第 2 型糖尿病大白鼠肝臟 glucose-6-phosphatase/hexokinase ratio、降低肝醣含量及降低胰島素阻抗指標 HOMA-IR 值，然而 D7C 及 D7CA 其肝臟三酸甘油酯及總膽固醇含量較少，且肝臟 acetyl-CoA carboxylase 活性也較 D 組低，而糞便膽酸排出量增加。D7CA 與 D7C 相比，更能顯著降低其肝臟總膽固醇及膽固醇酯含量，但減少每日糞便排出量及糞便脂質含量且對於血漿或肝臟脂質過氧化物濃度無影響。綜合以上，顯示 16 週給予幾丁聚醣或合併維生素 C 能改善第 2 型糖尿病大白鼠餐後血糖異常，20 週後對於其禁食血糖及血總膽固醇無影響，但於肝臟脂質異常有改善，且維生素 C 的添加更能降低肝臟脂質及改善胰島素阻抗情形，但會增加肝臟肝醣分解、減少每日糞便排出量及糞便脂質含量。

In this study, male Sprague-Dawely rats were injected by streptozotocin and nicotinamide to induce type 2 diabetes. Rats were divided into four group: Normal control (N), diabetes control (D), diabetes fed with 7% high molecular weight chitosan (D7C) and diabetes fed with 7% high molecular weight chitosan and 0.5% sodium ascorbate (D7CA). 0.5% cholesterol diet was supplemented to the experimental for 20 weeks. The results showed D7C and D7CA groups significantly decreased fasting plasma total cholesterol level when rats fed experimental diet 4 weeks. D7C group significantly decreased 30, 60 and 120 min plasma glucose after oral glucose tolerance test in fed experimental diet 9 and 16 weeks. D7CA group significantly decreased 60 min plasma glucose after oral glucose tolerance test in fed experimental diet 16 weeks. When 20 weeks, fasting plasma glucose and total cholesterol were not affected by chitosan and sodium ascorbate, but D7C group significantly increased fasting plasma triglyceride and plasma very low density lipoprotein cholesterol level, and significantly decreased lipoprotein lipase activity of perirenal adipose tissue. After 20 weeks, D7CA increased hepatic glucose-6-phosphatase/hexokinase ratio, reduced hepatic glycogen contents and HOMA-IR value. However, D7C and D7CA significantly decreased hepatic triglyceride and total cholesterol contents, lowered hepatic acetyl-CoA carboxylase activity, increased fecal bile acids. Compared with D7C, D7CA significantly lowered hepatic total cholesterol and cholesteryl ester contents, but had less fecal total cholesterol and bile acids. In summary, long term feeding chitosan and sodium ascorbate improved postprandial plasma glucose for 16 weeks and hepatic lipid disorder, but not fasting plasma glucose and lipid for 20 weeks. Furthermore, sodium ascorbate can lower hepatic lipid and improve insulin resistance by chitosan, but raised hepatic glycogenolysis, decreased daily feces excretion and fecal lipid.

目錄
第一章、前言………………………………………………………………… 1
第二章、文獻整理…………………………………………………………… 2
第一節、幾丁質和幾丁聚醣………………………………………………… 2
一、結構與來源……………………………………………………………… 2
二、製備與應用……………………………………………………………… 3
三、生理活性………………………………………………………………… 6
第二節、糖尿病……………………………………………………………… 6
一、糖尿病的定義與診斷標準……………………………………………… 7
二、糖尿病的分類…………………………………………………………… 9
三、糖尿病之併發症和治療………………………………………………… 11
四、第 2 型糖尿病動物誘導模式………………………………………… 12
五、糖尿病的糖代謝與脂質代謝…………………………………………… 16
六、維生素 C 對糖尿病的影響…………………………………………… 17
第三節、幾丁聚醣對糖尿病的影響………………………………………… 20
一、對糖代謝的影響………………………………………………………… 20
二、對脂質代謝的影響……………………………………………………… 20
三、維生素 C 的添加……………………………………………………… 21
第四節、脂蛋白代謝………………………………………………………… 23
第五節、醣類與脂質代謝的調節…………………………………………… 24
第三章、實驗動機與目的…………………………………………………… 26
第四章、材料與方法………………………………………………………… 27
第一節、幾丁聚醣…………………………………………………………… 27
第二節、實驗動物…………………………………………………………… 29
第三節、飼料配製…………………………………………………………… 29
第四節、動物分組…………………………………………………………… 29
第五節、動物飼養與樣品收集……………………………………………… 30
第六節、樣品分析…………………………………………………………… 31
第七節、統計分析…………………………………………………………… 53
第八節、實驗流程…………………………………………………………… 53
第五章、結果………………………………………………………………… 55
第一節、口服葡萄糖耐受性試驗…………………………………………… 55
一、誘導後 1 週進行口服葡萄糖耐受性試驗…………………………… 55
二、給予實驗飼料 9 週後進行口服葡萄糖耐受性試驗………………… 55
三、給予實驗飼料 16 週後進行口服葡萄糖耐受性試驗……………… 55
第二節、體重、攝食、飲水、排尿量及組織臟器重量變化…………… 55
一、實驗期間各週體重及體重變化量…………………………………… 55
二、實驗期間攝食、飲水及排尿量變化………………………………… 56
三、大白鼠組織臟器重量變化…………………………………………… 56
第三節、血漿分析………………………………………………………… 56
一、實驗期間禁食血漿總膽固醇及三酸甘油酯含量變化……………… 56
二、實驗 20 週後大白鼠犧牲血糖相關參數及肝醣…………………… 56
三、實驗 20 週後大白鼠犧牲血脂相關參數…………………………… 57
四、實驗 20 週後大白鼠犧牲血漿極低密度脂蛋白 (VLDL) 組成……… 57
五、實驗 20 週後大白鼠肝腎功能相關參數…………………………… 57
第四節、肝臟分析………………………………………………………… 58
一、實驗 20 週後大白鼠犧牲肝臟脂質相關參數……………………… 58
二、實驗 20 週後大白鼠犧牲肝臟醣類與脂質代謝相關酵素………… 58
第五節、腸道、脂肪及糞便分析…………………………………………… 58
一、實驗 20 週後大白鼠小腸雙醣酶活性……………………………… 58
二、實驗 20 週後大白鼠脂肪組織脂蛋白脂解酶活性及脂解速率…… 58
三、實驗 20 週後大白鼠糞便脂質相關參數…………………………… 59
第六章、討論………………………………………………………………… 60
第一節、對第 2 型糖尿病大白鼠醣類代謝之影響……………………… 60
第二節、對第 2 型糖尿病大白鼠脂質代謝之影響……………………… 62
第三節、對第 2 型糖尿病大白鼠肝腎功能之影響……………………… 65
第四節、總結………………………………………………………………… 66
第七章、結論………………………………………………………………… 67
第八章、參考文獻…………………………………………………………… 68

圖目錄
圖一、皮下注射 nicotinamide 與 streptozotocin 1 週後，正常與第 2 型糖尿病大白鼠進行口服葡萄糖耐受性試驗血糖之變化。……………………… 81
圖二、攝取不同實驗飼料 9 週後，正常與第 2 型糖尿病大白鼠進行口服葡萄糖耐受性試驗血糖之變化。………………………………………………… 82
圖三、攝取不同實驗飼料 16 週後，正常與第 2 型糖尿病大白鼠進行口服葡萄糖耐受性試驗血糖之變化。……………………………………………… 83
圖四、正常與第 2 型糖尿病大白鼠實驗期間各週體重及體重變化量。… 84
圖五、攝取不同實驗飼料二十週後，正常與第 2 型糖尿病大白鼠攝食量、飲水量及排尿量變化。………………………………………………………… 85
圖六、攝取不同實驗飼料二十週後，正常與第 2 型糖尿病大白鼠相對臟器重量之變化。…………………………………………………………………… 86
圖七、攝取不同實驗飼料 20 週後，正常與第 2 型糖尿病大白鼠禁食血漿總膽固醇及三酸甘油酯含量之變化。………………………………………… 87
圖八、攝食不同實驗飼料二十週後，正常與第 2 型糖尿病大白鼠小腸雙醣酶酵素活性之變化。…………………………………………………………… 94
圖九、正常與第 2 型糖尿病大鼠脂肪組織的脂蛋白脂解酶活性及脂解速率變化。………………………………………………………………………… 95

表目錄
表一、實驗飼料組成 (%)…………………………………………………… 80
表二、攝食不同實驗飼料二十週後，正常與第 2 型糖尿病大白鼠血糖相關參數及肝醣。…………………………………………………………………… 88
表三、攝食不同實驗飼料二十週後，正常與第 2 型糖尿病大白鼠血脂相關參數。………………………………………………………………………… 89
表四、攝食不同實驗飼料二十週後，正常與第 2 型糖尿病大白鼠血漿極低密度脂蛋白組成。……………………………………………………………… 90
表五、攝食不同實驗飼料二十週後，正常與第 2 型糖尿病大白鼠肝腎功能相關參數。………………………………………………………………………… 91
表六、攝食不同實驗飼料二十週後，正常與第 2 型糖尿病大白鼠肝臟脂質相關參數。………………………………………………………………………… 92
表七、攝食不同實驗飼料二十週後，正常與第 2 型糖尿病大白鼠肝臟醣類與脂質代謝酵素相關參數。…………………………………………………… 93
表八、攝取不同實驗飼料二十週後，正常與第 2 型糖尿病大白鼠糞便重量、糞便脂質和糞便膽酸之變化。……………………………………………… 96

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