臺灣博碩士論文加值系統

糖尿病是一種代謝性疾病，並與慢性發炎及氧化壓力的上升息息相關。芥子酸(sinapic acid; SA)為肉桂酸(cinnamic acid)的衍生物，並具有抗發炎及抗氧化的能力。然而，芥子酸與糖尿病之間的相關性仍不清楚。在本研究中，我們發現口服給予STZ誘發的糖尿病鼠芥子酸後，會具有降血糖的作用，同時會增加血中β-腦內啡(β-endorphin)的濃度。過去文獻證實，活化腎上腺髓質上的α1-腎上腺素受體(α1-AR)，會促使β-腦內啡的釋放，其透過活化嗎啡μ型受體而產生降血糖的作用。而芥子酸的降血糖作用，能明顯受α1-腎上腺素受體阻斷劑(prazosin)、嗎啡受體阻斷劑(naloxone)及特異性嗎啡μ型受體阻斷劑(nalonxonazine)所抑制。同時，已知β-腦內啡具有增加第四型骨骼肌葡萄糖轉運蛋白(GLUT4)基因的表現及降低肝臟中的磷酸烯醇式丙酮酸羧激?(PEPCK)基因的表現。在我們實驗中，以芥子酸治療STZ誘發的糖尿病鼠三天後，能提升骨骼肌的GLUT4及降低肝臟PEPCK的表現。此外，活化骨骼肌上的α1-腎上腺素受體會透過PLC-PKC的路徑，增加對葡萄糖的攝取。由芥子酸所刺激的葡萄糖攝取可被prazosin, U73122 及 chelerythrin所抑制。這些結果顯示，芥子酸能透過活化α1-AR，增加β-腦內啡的釋放，進一步加強骨骼肌對葡萄糖的攝取，及降低肝臟醣質新生，而達到降血糖的作用。

Diabetes is a metabolic disorder associated with chronic inflammation and increased oxidative stress. Sinapic acid (SA) is a cinnamic acid derivative that has anti-inflammatory and anti-oxidative capacities. However, the effects of SA on diabetes remain unclear. In the present study, we found that oral administration of SA in streptozocin-induced diabetic rats exerted a blood glucose lowering effect while increased plasma β-endorphin was also observed. Previous studies have been demonstrated that activation of α1-adrenoceptor (α1-AR) in adrenal gland is responsible for β-endorphin secretion, which exerted a function to decrease blood glucose through activation of opioid μ-receptor. The plasma glucose-lowering action of SA was markedly blocked by α1-ARs antagonist (prazosin), opioid receptor antagonist (naloxone) and specific opioid μ-receptor antagonist (nalonxonazine). Also, β-endorphin is known to increase skeletal muscle glucose transporter type 4 (GLUT4) gene expression and attenuate hepatic phosphoenolpyruvatecarboxykinase (PEPCK) gene expression. In our study, administration of SA for 3 days in STZ-induced diabetic rats elevated GLUT4 in muscle and decrease PEPCK expression in liver. In addition, activation of α1-AR increased glucose uptake in isolated skeletal muscle through a PLC-PKC dependent pathway. The SA-induced glucose uptake was blocked by prazosin, U73122 and chelerythrin in mouse skeletal fibroblast cells (C2C12). These results suggested that SA has an ability to decrease blood glucose through activation of α1-AR to increase β-endorphin secretion and this effect further enhance glucose uptake in muscle and decrease hepatic gluconeogenesis.

英文摘要 Ⅰ
中文摘要 Ⅲ
縮寫表 Ⅴ
第一章 緒論 1
第二章 實驗方法與材料 7
第三章 實驗結果 32
第四章 討論 41
第五章 結論 48
參考文獻 51
附圖 58
自述 75

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