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| ???org.dspace.app.webui.jsptag.ItemTag.dcfield??? | Value | Language |
|---|---|---|
| dc.contributor.advisor | 吳瑞碧 | |
| dc.contributor.author | Da-Wei Huang | en |
| dc.contributor.author | 黃大維 | zh_TW |
| dc.date.accessioned | 2021-06-15T04:11:54Z | - |
| dc.date.available | 2013-02-04 | |
| dc.date.copyright | 2010-02-04 | |
| dc.date.issued | 2010 | |
| dc.date.submitted | 2010-01-26 | |
| dc.identifier.citation | 何橈通。糖尿病與公共衛生。臨床醫學。1986。17: 300-317。
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/45274 | - |
| dc.description.abstract | 糖尿病為胰島素分泌缺乏或胰島素作用缺失所導致的一種醣類代謝的慢性疾病。約 95％ 的糖尿病患者屬於第二型糖尿病，發生原因主要為胰島素作用缺失及體內細胞對胰島素無法引起正常之反應而導致高血糖症。咖啡酸及肉桂酸為多種水果、蔬菜及咖啡中常存在的兩種酚酸，近來已有許多研究在評估此兩酚酸抗高血糖之活性。
本實驗以 TNF-α 誘導小鼠肝臟 FL83B 細胞產生胰島素阻抗，再評估咖啡酸及肉桂酸之增加阻抗細胞葡萄糖攝入及改善醣類代謝。實驗中以葡萄糖攝入實驗評估兩種酚酸降血糖之效果，並分析胰島素訊息蛋白、肝醣合成相關酵素以及糖質新生酵素的表現，以解釋胰島素阻抗 FL83B 細胞中葡萄糖攝入增加與肝醣合成之改善。 於抗高血糖效果實驗中發現，咖啡酸及肉桂酸會促進胰島素受器 (Insulin receptor, IR) 磷酸化及增加胰島素訊息相關蛋白包括磷酸肌醇激酶(phosphatidylinositol-3 kinase, PI3K)、肝醣合成酶 (glycogen synthase, GS) 及葡萄糖轉運蛋白 (glucose transporter-2, GLUT-2) 的表現。於改善醣類代謝結果顯示，此兩種酚酸會增加胰島素阻抗細胞中葡萄糖激酶 (Glucokinase, GK)，但會減少肝醣合成酶激酶 (glycogen synthase kinase, GSK)、肝醣合成酶 serine 磷酸、肝細胞核因子 (hepatic nuclear factor-4, HNF-4) 及磷酸烯醇式丙酮酸羧激酶(phosphoenolpyruvate carbooxykinase, PEPCK) 的表現。根據以上之結果推測，咖啡酸及肉桂酸可以藉由改善胰島素阻抗 FL83B 細胞對胰島素的敏感度而促進細胞葡萄糖攝入及改善醣類代謝。 | zh_TW |
| dc.description.abstract | Diabetes mellitus (DM) is a chronic disease associated with carbohydrate metabolism and caused by a deficiency in insulin secretion or by the ineffectiveness in insulin action. About 95% of the diabetic incidences belong to type 2 diabetes, of which the main cause of hyperglycemia is the ineffectiveness in insulin action or the inability to induce a normal response to insulin in the cells. Two phenolic acids, caffeic acid and cinnamic acid, are commonly present in fruits, vegetables, and coffee. Anti-hyperglycemic activity has become a focus in recent studies on these two phenolic acids.
The present study investigated the effect of the two phenolics on enhancing glucose uptake and ameliorating carbohydrate metabolism in TNF-α-induced insulin resistant mouse liver FL83B cells.The uptake test of 2-[1-14C ] deoxy-D-glucose in insulin resistant FL83B cells was performed to evaluate the hypoglycemic effect. The expressions of insulin signal proteins, glycogen synthesis associated enzymes and the enzymes of gluconeogenesis were analyzed to elucidate the enhancement on glucose uptake and the restoration on glycogen synthesis in insulin resistant FL83B cells by the phenolic acids.. In the results of antihyperglycemic effect, the two phenolic acids promote insulin receptor tyrosyl phosphorylation, up-regulat the expression of insulin signal associated proteins, including insulin receptor, phosphatidylinositol-3 kinase (PI3K), glycogen synthase (GS), and glucose transporter-2 (GLUT-2). The results of amelioration on carbohydrate metabolism revealed that the two phenolic acids increase the expression of Glucokinase (GK), while decrease the expression of glycogen synthase kinase (GSK), Ser-641 phosphorylation of GS, hepatic nuclear factor-4 (HNF-4), and phosphoenolpyruvate carbooxykinase (PEPCK) in the resistant cells. In conclusion, we speculate that caffeic acid and cinnamic acid may improve glucose uptake and ameliorate carbohydrate metabolism by restoring isulin sensitivity in insulin resistant FL83B cells. These two phenolic acids may restore glycogen synthesis, promote glucose uptake into cells, inhibit gluconeogehesis to decrease glucose formation, and result in the alleviation of insulin resistance in cells as the consequence. | en |
| dc.description.provenance | Made available in DSpace on 2021-06-15T04:11:54Z (GMT). No. of bitstreams: 1 ntu-99-D94641002-1.pdf: 1384172 bytes, checksum: 2e1bf4ea65417aa51e60dc81b76179a3 (MD5) Previous issue date: 2010 | en |
| dc.description.tableofcontents | 中文摘要 ..……………………………………………………………………I
英文摘要 ..……………………………………………………………………II 目錄 ..…………………………………………………………………….IV 圖次 ..…………………………………………………………………………VII 表次 ..…………………………………………………………………………VIII 緒論 ..……………………………………………………………………… 1 第一章 文獻回顧 ..…………………………………………………………….3 第ㄧ節 糖尿病 ……………………………………………………………3 一、糖尿病的流行病學 ..………………………………………………… 3 二、糖尿病簡介 ..………………………………………………………… 3 三、糖尿病分類 ..………………………………………………………… 4 第二節 胰島素 ..……………………………………………………………8 一、胰島素簡介 ..………………………………………………………… 8 二、胰島素的作用 ..……………………………………………………… 8 三、胰島素在細胞層次之作用 ..………………………………………… 10 四、胰島素的訊息傳遞 ..………………………………………………… 12 五、胰島素與糖類代謝 ..………………………………………………… 17 第三節 胰島素阻 ..…………………………………………………………. 19 一、胰島素阻抗之病因 ..………………………………………………… 19 二、胰島素阻抗性之定義 ..……………………………………………… 19 三、Tumor necrosis factor-α 與胰島素阻抗 ..…………………………...21 四、以細胞模式探討胰島素阻抗之研究 ..………………………………23 第四節 抗糖尿病物質 ..…………………………………………………….26 一、常見抗糖尿病藥物 ..…………………………………………………26 二、新上市之降血糖藥物 ..……………………………………………… 29 第五節 酚酸抗糖尿病之研究 .…………………………………………….31 一、酚酸之介紹 ..………………………………………………………… 31 二、酚酸抗糖尿病 ..……………………………………………………… 31 第二章 研究動機與實驗架構 ..……………………………………………….35 第三章 咖啡酸與肉桂酸促進葡萄糖攝入及機制之探討 ..………………….37 第一節 前言 .……………………………………………………………….37 第二節 實驗材料 ..…………………………………………………………. 38 ㄧ、實驗樣品來源 ..………………………………………………………38 二、實驗細胞 ..…………………………………………………………… 38 三、實驗藥品及試劑 ..…………………………………………………… 38 四、實驗藥品配製 ...……………………………………………………… 39 五、儀器設備 ..…………………………………………………………… 41 第三節 實驗方法 ..…………………………………………………………. 42 ㄧ、TNF-α 誘導FL83B細胞胰島素阻抗之評估 ..……………… 42 二、FL83B 細胞對葡萄糖之攝入作用 ..………………………… 42 三、西方轉印分析細胞處理及蛋白質萃取 ..…………………… 43 四、西方轉印分析 ..……………………………………………… 43 五、統計分析 ..………………………………………………… 46 第四節 結果與討論 ..…………………………………………. 47 ㄧ、TNF-α 誘導 FL83B 細胞胰島素阻抗 ..…………………… 47 二、酚酸對具胰島素阻抗 FL83B 細胞葡萄糖攝入之影響 ..… 48 三、高濃度咖啡酸及肉桂酸對具胰島素阻抗 FL83B 細胞葡萄糖攝入之影響 ..………………………………………………...48 四、低濃度咖啡酸及肉桂酸對具胰島素阻抗 FL83B 細胞葡萄糖攝入之影響 ..………………………………………………………… 49 五、咖啡酸及肉桂酸於胰島素阻抗 FL83B 細胞葡萄糖攝入之影響 .. 49 六、咖啡酸及肉桂酸於胰島素阻抗 FL83B 細胞胰島素訊息之影響 .. 51 (一) 胰島素受體表現及其酪胺酸磷酸化 ..………………… 51 (二) 磷酸肌醇激酶表現 ..……………………………………… 52 (三) 肝醣合成酶及葡萄糖轉運蛋白表現 ..…………………………53 第五節 結論 ..……………………………………………………… 55 第四章 咖啡酸與肉桂酸促進肝醣合成及改善醣類代謝之探討 ………… 68 第一節 前言 ..…………………………………………… 68 第二節 實驗材料 ..…………………………………………… 69 ㄧ、實驗樣品來源 ..………………………………………… 69 二、實驗細胞 ..……………………………………………… 69 三、實驗藥品及試劑 .…………………………………………… 69 四、實驗藥品配製 ..………………………………………… 70 五、儀器設備 ..………………………………………………… 70 第三節 實驗方法 ..……………………………………………. 71 ㄧ、FL83B細胞中肝醣含量之測定 .………………………… 71 二、西方轉印分析細胞處理及蛋白質萃取 ..………………… 71 三、西方轉印分析 ..…………………………………………… 72 四、FL83B細胞中phosphoenolpyruvate carboxylase 活性測定 ..…….. 72 五、統計分析 ..………………………………………………… 72 第四節 結果與討論 ..………………………………………… 73 一、咖啡酸及肉桂酸對胰島素阻抗 FL83B 細胞肝醣含量之影響 … 73 二、咖啡酸及肉桂酸對胰島素阻抗 FL83B 細胞葡萄糖激酶之影響 .. 74 三、咖啡酸及肉桂酸對胰島素阻抗 FL83B 細胞肝醣合成酶磷酸化之影響 ..………………………………………………………… 75 四、咖啡酸及肉桂酸對胰島素阻抗 FL83B 細胞肝醣合成酶激酶-3 之影響 ..………………………………………………………… 76 五、咖啡酸及肉桂酸對胰島素阻抗 FL83B 細胞醣質新生之影響…… 78 第五節 結論 ..………………………………………………… 81 第五章 總結 ..…………………………………………………………………… 91 參考文獻 ..……………………………………………………………………. 93 圖 次 圖 1-1、糖尿病的分類 ..……………………………………………………… 7 圖 1-2、胰島素調節之代謝作用 ...…………………………… 9 圖 1-3、肝臟及肌肉中肝醣代謝示意圖 ……………………... 11 圖 1-4、胰島素訊息傳遞示意圖 ..…………………………… 13 圖 1-5、肝臟葡萄糖代謝之調節 ..……………………… 18 圖 1-6、(a) 胰島素於正常狀態調節葡萄糖平衡之作用 (b) 胰島素阻抗狀態造成之現象…………………………20 圖 1-7、TNF-α 減少 IRS-1 serine phosphorylation 的可能原因 ..…….22 圖 1-8、Hydroxybenzoic acid 及 Hydroxycinnamic acid 之化學結構 ……. 33 圖 1-9、綠原酸及咖啡酸之化學結構 ……………………. 34 圖 2-1、實驗架構 …………………………………………… 36 圖 3-1、TNF-α 抑制小鼠肝臟 FL83B 細胞葡萄糖攝入 ……… 56 圖 3-2、不同酚酸 (50 μM) 對具胰島素阻抗 FL83B 細胞葡萄糖攝入之影響 …………………………………………………. 57 圖 3-3、高濃度之咖啡酸對具胰島素阻抗 FL83B 細胞葡萄糖攝入之影響 58 圖 3-4、高濃度之肉桂酸對具胰島素阻抗 FL83B 細胞葡萄糖攝入之影響 59 圖 3-5、低濃度之咖啡酸對具胰島素阻抗 FL83B 細胞葡萄糖攝入之影響 60 圖 3-6、低濃度之肉桂酸對具胰島素阻抗 FL83B 細胞葡萄糖攝入之影響 61 圖 3-7、咖啡酸及肉桂酸對 TNF-α 誘導胰島素阻抗 FL83B 細胞葡萄糖攝入之影響 …………………………………………...…62 圖 3-8、咖啡酸及肉桂酸對 TNF-α 誘導胰島素阻抗 FL83B 細胞胰島素受器表現之影響 ……………………………………………… 63 圖 3-9、咖啡酸及肉桂酸對 TNF-α 誘導胰島素阻抗 FL83B 細胞胰島素受器磷酸化之影響 …………………………………………. 64 圖 3-10、咖啡酸及肉桂酸對 TNF-α 誘導胰島素阻抗 FL83B 細胞 PI3K 表現之影響 ………………………………………………. 65 圖 3-11、咖啡酸及肉桂酸對 TNF-α 誘導胰島素阻抗 FL83B 細胞肝醣合成酶表現之影響 …………………………………………… 66 圖 3-12、咖啡酸及肉桂酸對 TNF-α 誘導胰島素阻抗 FL83B 細胞葡萄糖轉運蛋白表現之影響……………………………………………67 圖 4-1、肝醣含量之標準曲線 …………………………………… 82 圖 4-2、FL83B細胞於不同處理下肝醣之含量 ………………….83 圖 4-3、咖啡酸及肉桂酸對 TNF-α 誘導胰島素阻抗 FL83B 細胞葡萄糖激酶表現之影響 ……………………………………………… 84 圖 4-4、咖啡酸及肉桂酸對 TNF-α 誘導胰島素阻抗 FL83B 細胞肝醣合成酶表現之影響 ……………………………………………… 85 圖 4-5、咖啡酸及肉桂酸對 TNF-α 誘導胰島素阻抗 FL83B 細胞肝醣合成酶 serine 磷酸化之影響 ………………………………… 86. 圖 4-6、咖啡酸及肉桂酸對 TNF-α 誘導胰島素阻抗 FL83B 細胞 glycogen synthase kinase-3α 之影響 ………………………… 87 圖 4-7、咖啡酸及肉桂酸對 TNF-α 誘導胰島素阻抗 FL83B 細胞 glycogen synthase kinase-3β 之影響 ………………………… 88 圖 4-8、咖啡酸及肉桂酸對 TNF-α 誘導胰島素阻抗 FL83B 細胞 hepatic nuclear factor-4 之影響……………………………… 89. 圖 4-9、咖啡酸及肉桂酸對 TNF-α 誘導胰島素阻抗 FL83B 細胞 phosphoenolpyruvate carboxylase 之影響 ………………………90 圖 5-1、咖啡酸及肉桂酸減緩 FL83B 細胞胰島素阻抗可能之機制 ...…………………………………………… 92 表 次 表 1-1、輔助性葡萄糖轉運蛋白種類 ……………………… 16 | |
| dc.language.iso | zh-TW | |
| dc.title | 咖啡酸及肉桂酸減輕小鼠肝臟細胞 (FL83B) 胰島素阻抗及改善碳水化合物代謝之研究 | zh_TW |
| dc.title | Alleviation of Insulin Resistance and Improvement in Carbohydrate Metabolism in Insulin Resistant Mouse Liver FL83B Cells by Caffeic acid and Cinnamic acid | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 98-1 | |
| dc.description.degree | 博士 | |
| dc.contributor.coadvisor | 沈賜川 | |
| dc.contributor.oralexamcommittee | 鄭瑞棠,陳水田,吳明昌,江孟燦,廖慧芬,馬嘉軉 | |
| dc.subject.keyword | 糖尿病,咖啡酸,肉桂酸,葡萄糖攝入,肝醣合成,胰島素阻抗, | zh_TW |
| dc.subject.keyword | Diabetes mellitus,caffeic acid,cinnamic acid,glucose uptake,glycogen synthesis,insulin resistance, | en |
| dc.relation.page | 105 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2010-01-26 | |
| dc.contributor.author-college | 生物資源暨農學院 | zh_TW |
| dc.contributor.author-dept | 食品科技研究所 | zh_TW |
| dc.date.embargo-lift | 2300-01-01 | - |
| Appears in Collections: | 食品科技研究所 | |
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