|Abstract: ||本研究主要探討高、低分子量幾丁聚醣對於streptozotocin (STZ) 誘導後所形成的第一型糖尿病 Sprague-Dawley (SD) 大白鼠其醣代謝的機制。實驗總共分成四組：(1) 正常組添加 5% cellulose (2) 第一型糖尿病組添加 5% cellulose (3) 第一型糖尿病組添加 5% 高分子量幾丁聚醣 (4) 第一型糖尿病組添加 5% 低分子量幾丁聚醣；結果發現，在肝臟重量方面，高、低分子量幾丁聚醣的組別其重量皆比糖尿病控制組低，而在脂肪組織重量方面，低分子量幾丁聚醣組則比糖尿病控制組高。血漿生化值方面，高、低分子量幾丁聚醣皆會明顯降低血漿中血糖及果糖胺，在胰島素濃度方面則無顯著差異，高分子量幾丁聚醣的組別其 HOMA-IR 值相較於糖尿病控制組有顯著下降。在血脂濃度方面，高、低分子量幾丁聚醣能有效降低第一型糖尿病大白鼠血漿中總膽固醇的含量，然而在三酸甘油酯和游離脂肪酸方面，則無統計的差異。另外，測定大鼠血漿腫瘤壞死因子 (Tumor necrosis factor, TNF-) 後，結果顯示各組間並無顯著差異；而在血漿中瘦體素 (Leptin) 的含量方面，高、低分子量幾丁聚醣的組別皆會明顯升高，其中又以低分子量幾丁聚醣的組別上升量最為顯著。纖維蛋白溶酶原活化抑制劑-1 (Plasminogen activator inhibitor type 1, PAI-1) 主要參與血液的凝集反應，實驗結果發現，高、低分子量幾丁聚醣皆會降低血漿中 PAI-1 的濃度。在蛋白表現量的部份，肝臟中糖質新生的關鍵酵素 phosphoenolpyruvate carboxykinase (PEPCK) 在低分子量幾丁聚醣的組別有明顯的下降；而 AMP-activated protein kinase (AMPK) 主要會控制體內能量的恆定，實驗結果發現高、低分子量幾丁聚醣的組別 AMPK 的磷酸化明顯提高許多；另外在 p38 mitogen-activated protein kinase (p38 MAPK) 方面，由實驗結果可得知，高、低分子量幾丁聚醣的組別其磷酸化的現象明顯被抑制；UCP2 是一個位於粒線體內膜上的轉運蛋白，根據實驗數據顯示，四組間並無顯著差異。另外測定肝臟中肝醣含量，發現餵食幾丁聚醣的組別相較於糖尿病控制組有明顯的增加。在肌肉中，高、低分子量幾丁聚醣的組別其 Akt 與 GLUT4 的表現量皆顯著提升。綜合以上結果，推測幾丁聚醣能有效改善組織對葡萄糖的利用，進而降低血糖。|
This study was designed to investigate the effects of high and low molecular weight chitosan on carbohydrate metabolism in streptozotocin-induced type 1 diabetic rats. The experiments were separated into four groups: (1) normal rats with 5% cellulose, (2) type 1 diabetic rats with 5% cellulose, (3) type 1 diabetic rats with 5% high molecular weight chitosan, (4) type 1 diabetic rats with 5% low molecular weight chitosan. As the results, both high and low molecular weight chitosan groups were lower than type 1 diabetic group in liver weight. In addition, low molecular weight chitosan group was higher than type 1 diabetic group in adipose tissue quantity. In these plasma biological values, we found that both high and low molecular weight chitosan groups were significantly reduced blood glucose, insulin, HOMA-IR, and fructosamine in plasma. In plasma lipid concentration, high and low molecular weight chitosan groups reduced the plasma total cholesterol in type 1 diabetic rats, however, they were no significant difference on triglyceride concentration and free fatty acids. Furthermore, TNF-concentration was no significant difference in each group. On the other hand, in plasma leptin content, both high and low molecular weight chitosan groups raised obviously, and low molecular weight chitosan group was the highest. PAI-1 which mainly participated into agglutination system, from our results showed that high and low molecular weight chitosan groups both decreased PAI-1 content in plasma. On the protein level, PEPCK which is the hepatic key enzyme in gluconeogenesis had an abvious decrease in low molecular weight chitosan group. AMPK maintain the energy homeostasis, and the experimental result showed the phosphorylation of AMPK raised significantly in both high low molecular weight chitosan groups. In addition, we found that phosphorylation of p38 MAPK was inhibited in high and low molecular weight chitosan groups. UCP2 which is a transporter on mitochondria inner membrane had no significance from the experimental result. We also found the hepatic glycogen was increased in high and low molecular weight chitosan groups. In skeletal muscle, we knew the results from these experiments, akt and GLUT4 expression were elevated obviously in high and low molecular weight chitosan groups. Together, our results from present study suggest that chitosan may improve glucose uptake in peripheral tissues, thus decreasing plasma glucose.