請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/82013完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 周綠蘋(Lu-Ping Chow) | |
| dc.contributor.author | Shuo-Chun Zhang | en |
| dc.contributor.author | 張碩純 | zh_TW |
| dc.date.accessioned | 2022-11-25T05:34:05Z | - |
| dc.date.available | 2026-08-12 | |
| dc.date.copyright | 2021-08-31 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-08-13 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/82013 | - |
| dc.description.abstract | 胰臟癌 (PC) 高居目前全球癌症死亡統計中第七位、而其五年存活率則位居末位。由於胰臟癌本身缺乏顯著病徵，故導致難以診斷，超過八成以上的患者在確診時皆已進展到手術無法切除的晚期階段。根據研究指出，超過四成以上的患者在確診前，會因胰臟癌所釋放出的致糖尿病因子產生新生糖尿病的症狀，而若能將胰臟癌所導致的新生糖尿病 (PCDM) 與第二型糖尿病進行區分，便有利於作為胰臟癌的早期診斷。而本實驗室透過質譜分析、生物資訊學分析、及細胞功能測試，發現 galectin-3 可作為 PCDM 有力的生物標記物。 為了進一步了解 galectin-3 在 PCDM 所調控的機轉，我們首先利用自行純化的重組蛋白 galectin-3 針對肌肉細胞進行實驗，發現 galectin-3 藉由增加 IRS-1 的抑制性絲氨酸磷酸化和降低 Akt 的活性來抑制胰島素訊息傳導路徑。從免疫共沉澱實驗也可見 galectin-3 與肌肉細胞的 TLR4 受體具有交互作用，由此可知，galectin-3 透過與 TLR4 結合進而活化 IKK-β/NF-κB 路徑，並且活化 IRS-1 Ser307 、降低 AKT 的磷酸化，因而導致肌肉細胞的胰島素訊息傳導路徑受阻、進一步發生胰島素阻抗。 另一方面探討 galectin-3 對於胰島 β 細胞功能障礙的調控。實驗結果顯示，galectin-3可使胰島 β 細胞存活率下降。深入探討其機制發現，galectin-3 會透過提升 IKK 與 ERK 的磷酸化，進而使促進細胞凋亡的相關分子，如：Bax/Bcl-2 比值與 cleaved caspase 3 表現量有所上升；而在 TLR4 或 IKK 抑制劑的處理之下，促進細胞凋亡的訊號則有所下降。除此之外，透過組織染色方式，我們也觀察到相較於 PC 患者，PCDM 患者的胰島中 cleaved caspase 3 表現量上升、胰島素分泌量下降，顯示 galectin-3 可藉由活化 TLR4/IKK 路徑，進一步誘使 ERK 引發胰島 β 細胞凋亡。 根據上述之結果，本篇論文釐清 galectin-3 作為 PCDM 的生物標記物在誘發糖尿病的機制上所扮演的角色，在肌肉細胞上，其可透過活化 TLR4/IKK 進而抑制胰島素訊息傳遞路徑來造成胰島素抗性；而在胰島 β 細胞上，則可透過活化 TLR4/IKK/ERK 路徑來誘導細胞凋亡，且在臨床上也顯示相同現象。 | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-25T05:34:05Z (GMT). No. of bitstreams: 1 U0001-0508202116084800.pdf: 3770566 bytes, checksum: 53e825e35ca1738acec105cff8cfa44c (MD5) Previous issue date: 2021 | en |
| dc.description.tableofcontents | 口試委員審定書------------------------------------------------------------------------------------------- I 謝誌--------------------------------------------------------------------------------------------------------- II 中文摘要-------------------------------------------------------------------------------------------------- III ABSTRACT---------------------------------------------------------------------------------------------- IV 縮寫-------------------------------------------------------------------------------------------------------- VI 目錄--------------------------------------------------------------------------------------------------------- 2 圖 目錄----------------------------------------------------------------------------------------------------- 3 附錄 目錄-------------------------------------------------------------------------------------------------- 4 第 一 章 導 論------------------------------------------------------------------------------------- 5 第 一 節 胰 臟 癌---------------------------------------------------------------------------------- 5 第 二 節 胰 臟 癌 誘 發 的 新 生 糖 尿 病 ( P C D M )------------------------------------ 10 第 三 節 生 物 標 記 物-------------------------------------------------------------------------- 12 第 四 節 G A L E C T I N – 3------------------------------------------------------------------- 13 第 五 節 胰 島 素 訊 息 傳 導 路 徑 與 胰 島 素 阻 抗------------------------------------ 15 第 六 節 研 究 動 機------------------------------------------------------------------------------ 18 第 二 章 實 驗 材 料---------------------------------------------------------------------------- 19 第 一 節 細 胞 株--------------------------------------------------------------------------------- 19 第 二 節 組 織 切 片 樣 本---------------------------------------------------------------------- 19 第 三 節 抗 體------------------------------------------------------------------------------------- 19 第 四 節 藥 品------------------------------------------------------------------------------------- 20 第 五 節 試 劑 組--------------------------------------------------------------------------------- 22 第 六 節 儀 器------------------------------------------------------------------------------------- 22 第 三 章 實 驗 方 法---------------------------------------------------------------------------- 24 第 一 節 細 胞 培 養------------------------------------------------------------------------------ 24 第 二 節 候 選 蛋 白 製 備---------------------------------------------------------------------- 25 第 三 節 蛋 白 質 分 析-------------------------------------------------------------------------- 26 第 四 節 細 胞 功 能 分 析---------------------------------------------------------------------- 31 第 五 節 細 胞 訊 息 傳 導 路 徑 分 析------------------------------------------------------- 33 第 六 節 臨 床 檢 體 分 析---------------------------------------------------------------------- 34 第 四 章 研 究 結 果---------------------------------------------------------------------------- 35 第 一 節 G A L E C T I N - 3 在 C 2 C 1 2 肌 肉 細 胞 中 調 控 的 機 制------------ 35 第 二 節 G A L E C T I N - 3 在 I N S - 1 胰 島 β 細 胞 中 調 控 的 機 制------------ 36 第 三 節 P C D M 胰 島 組 織 中 細 胞 凋 亡 現 象--------------------------------------- 38 第 五 章 討 論----------------------------------------------------------------------------------- 39 第 一 節 探 討 G A L E C T I N - 3 調 控 肌 肉 細 胞 中 胰 島 素 阻 抗 的 機 制--- 39 第 二 節 探 討 G A L E C T I N - 3 調 控 胰 島 β 細 胞 中 細 胞 凋 亡 的 機 制----- 41 第 三 節 探 討 P C D M 胰 島 組 織 中 細 胞 凋 亡 現 象-------------------------------- 43 第 四 節 未 來 展 望------------------------------------------------------------------------------ 44 參 考 文 獻------------------------------------------------------------------------------------------------ 45 圖----------------------------------------------------------------------------------------------------------- 53 附錄-------------------------------------------------------------------------------------------------------- 63 | |
| dc.language.iso | zh-TW | |
| dc.subject | 半乳糖凝集素-3 | zh_TW |
| dc.subject | 生物標記物 | zh_TW |
| dc.subject | 胰島素抗性 | zh_TW |
| dc.subject | 胰島 β 細胞凋亡 | zh_TW |
| dc.subject | 胰臟癌誘發之新生糖尿病 | zh_TW |
| dc.subject | β cell apoptosis | en |
| dc.subject | biomarker | en |
| dc.subject | galectin-3 | en |
| dc.subject | insulin resistance | en |
| dc.subject | PCDM | en |
| dc.title | 探討生物標記物 Galectin-3 於胰臟癌誘發新生糖尿病之調控機轉 | zh_TW |
| dc.title | Understanding the mechanism of biomarker galectin-3 in pancreatic cancer-associated new-onset diabetes (PCDM). | en |
| dc.date.schoolyear | 109-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 廖偉智(Hsin-Tsai Liu),周祖述(Chih-Yang Tseng),龔秀妮 | |
| dc.subject.keyword | 胰臟癌誘發之新生糖尿病,胰島素抗性,胰島 β 細胞凋亡,半乳糖凝集素-3,生物標記物, | zh_TW |
| dc.subject.keyword | PCDM,insulin resistance,β cell apoptosis,galectin-3,biomarker, | en |
| dc.relation.page | 67 | |
| dc.identifier.doi | 10.6342/NTU202102114 | |
| dc.rights.note | 同意授權(限校園內公開) | |
| dc.date.accepted | 2021-08-13 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 生物化學暨分子生物學研究所 | zh_TW |
| dc.date.embargo-lift | 2026-08-12 | - |
| 顯示於系所單位： | 生物化學暨分子生物學科研究所 | |
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| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| U0001-0508202116084800.pdf 未授權公開取用 | 3.68 MB | Adobe PDF | 檢視/開啟 |
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