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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 張以承 | zh_TW |
| dc.contributor.advisor | Yi-Cheng Chang | en |
| dc.contributor.author | 李婕熒 | zh_TW |
| dc.contributor.author | Jie-Ying Li | en |
| dc.date.accessioned | 2025-09-22T16:05:36Z | - |
| dc.date.available | 2025-09-23 | - |
| dc.date.copyright | 2025-09-22 | - |
| dc.date.issued | 2025 | - |
| dc.date.submitted | 2025-07-25 | - |
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Toledo, Skeletal Muscle Mitochondria in Insulin Resistance: Differences in Intermyofibrillar Versus Subsarcolemmal Subpopulations and Relationship to Metabolic Flexibility. The Journal of Clinical Endocrinology & Metabolism, 2011. 96(2): p. 494-503 | - |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/99944 | - |
| dc.description.abstract | 第二型糖尿病是一種常見的慢性代謝性疾病，其主要特徵之一是胰島素抵抗。然而，至今對胰島素抵抗的形成機制仍未有明確的定論。近年來的研究指出，粒線體功能異常與胰島素訊號傳遞障礙之間存在密切關聯，但兩者之間的因果關係及其調控機制仍待進一步釐清。
本研究聚焦於 SUPV3L1(SUV3)的功能與代謝異常之間的關係。SUV3是粒線體RNA降解體中的關鍵成員，主要負責粒線體內RNA的穩定性與代謝調節。在小鼠模型中，缺失SUV3會造成粒線體DNA的突變累積，進而引發粒線體功能受損，而這些異常可經由母系遺傳傳遞給下一代。 透過SUV3缺失小鼠模型，我們發現下一代在代謝功能上出現異常，包括葡萄糖耐受不良、胰島素敏感性下降，並且在骨骼肌中蛋白激酶(Akt)的磷酸化程度也顯著降低，顯示胰島素訊號傳遞路徑遭受干擾。同時，mtDNAmaternal mutation小鼠的血液中游離脂肪酸濃度偏高，並伴隨運動耐力下降。進一步利用間接熱量測量法分析其能量來源，發現mtDNAmaternal mutation小鼠在非運動狀態下的代謝偏好使用碳水化合物作為能量來源，且mtDNAmaternal mutation小鼠在脂肪酸代謝及電子傳遞鏈的活性也顯著降低，顯示粒線體功能受損對脂肪酸代謝產生影響。 綜上所述，我們認為 SUV3 的缺失不僅會損害粒線體功能，還會透過干擾肌肉細胞中的胰島素訊號傳遞而導致胰島素抵抗，進一步干擾代謝平衡。本研究提供了粒線體與胰島素抵抗之間可能機制的證據，也為未來探討粒線體相關疾病，特別是糖尿病的發病途徑提供了一個潛在的研究方向。 | zh_TW |
| dc.description.abstract | Type 2 diabetes is a prevalent chronic disease involving insulin resistance, with the cause of this resistance still not fully understood. Previous research has found a strong connection between insulin resistance and mitochondrial dysfunction and, but the casual relationship and specific mechanisms remain unclear. Recent studies highlight a strong association between mitochondrial dysfunction and impaired insulin signaling. However, the relationship and detailed molecular pathways are still under investigation. In this study, we chose to investigate the regulation of SUV3, which is a component of the mitochondrial RNA degradosome responsible for the metabolism and regulation of mitochondrial RNA. Deletion of SUV3 in mice can lead to mitochondrial DNA mutations and a decrease in mitochondrial function, and these phenotypes can be maternally inherited to the next generation. Our research found that mice inheriting mitochondrial DNA mutations could develop glucose intolerance and insulin resistance, along with a significant decrease in skeletal muscle Akt phosphorylation. We further revealed that mice inheriting mitochondrial DNA mutations maternally also have higher free fatty acid in the blood and decreased exercise tolerance. Indirect calorimetry measurements showed a reduced proportion of fatty acid burning in these mice. In addition, the activity of Fatty acid oxidation and oxidative phosphorylation are reduced mice with mitochondrial DNA mutation mice, suggesting that mitochondrial dysfunction affect β-oxidation. We found that SUV3 deletion leads to a decrease in Akt phosphorylation in skeletal muscle, affecting the insulin signaling pathway and thus causing insulin resistance. These new research findings can be beneficial to clinical studies for diabetes patients. | en |
| dc.description.provenance | Submitted by admin ntu (admin@lib.ntu.edu.tw) on 2025-09-22T16:05:35Z No. of bitstreams: 0 | en |
| dc.description.provenance | Made available in DSpace on 2025-09-22T16:05:36Z (GMT). No. of bitstreams: 0 | en |
| dc.description.tableofcontents | 口試委員審定書 i
致謝 ii 中文摘要 iii ABSTRACT iv 目次 vi 圖次 viii 第一章 引言 1 (一)、 糖尿病 1 (一)、 異位脂肪 2 (二)、 粒線體功能損壞 7 (三)、 SUV3基因功能 12 第二章 材料與方法 14 (一)、 動物模型： 14 (二)、 葡萄糖與胰島素耐受性測試 15 (三)、 體組成分析儀 16 (四)、 基因集富集分析(Gene Set Enrichment Analysis, GSEA) 16 (五)、 西方墨點分析(western blot analysis) 17 (六)、 運動測試 17 (七)、 血清生化 17 (八)、 間接熱量測定以測試能量消耗 20 (九)、 脂肪酸氧化實驗 20 (十)、 OXPHOS 酵素活性檢測 21 (十一)、 海馬生物能量測定儀(sea horse XF cell mito stress test) 26 (十二)、 肌肉切片、電子顯微鏡與粒線體型態的量化分析 27 (十三)、 萃取粒線體DNA 27 第三章 結果 30 (一)、 mtDNAmaternal mutation小鼠發展出胰島素抗性和葡萄糖耐受不良 30 (二)、 mtDNAmaternal mutation小鼠在GSEA顯示多條代謝基因表現下調 31 (三)、 mtDNAmaternal mutation小鼠耐力性運動表現較差 31 (四)、 mtDNAmaternal mutation小鼠具有更高的游離脂肪酸水平 31 (五)、 mtDNAmaternal mutation小鼠具有改變的燃料利用方式 32 (六)、 mtDNAmaternal mutation小鼠的β氧化代謝能力較差 32 (七)、 mtDNAmaternal mutation小鼠氧化磷酸化酵素活性下降且蛋白質表現量增強而代償效應 32 (八)、 mtDNAmaternal mutation小鼠產能效率降低 33 (九)、 mtDNAmaternal mutation小鼠在肌原纖維的粒線體面積小且數量多 33 第四章 討論 35 圖 39 第五章 參考資料： 47 | - |
| dc.language.iso | zh_TW | - |
| dc.subject | 胰島素阻抗性 | zh_TW |
| dc.subject | 第二型糖尿病 | zh_TW |
| dc.subject | 脂肪酸氧化 | zh_TW |
| dc.subject | 粒線體DNA | zh_TW |
| dc.subject | SUV3 | zh_TW |
| dc.subject | SUV3 | en |
| dc.subject | mitochondrial DNA | en |
| dc.subject | fatty acid oxidation | en |
| dc.subject | insulin resistance | en |
| dc.subject | Type 2 diabetes mellitus | en |
| dc.title | 攜帶母系遺傳突變粒線體的小鼠產生葡萄糖耐受不良與胰島素敏感性降低 | zh_TW |
| dc.title | Mice carrying maternally-inherited mutant mitochondria developed glucose intolerance and insulin sensitivity | en |
| dc.type | Thesis | - |
| dc.date.schoolyear | 113-2 | - |
| dc.description.degree | 碩士 | - |
| dc.contributor.oralexamcommittee | 劉雅雯;潘思樺 | zh_TW |
| dc.contributor.oralexamcommittee | Ya-Wen Liu;Sih-Hua Pan | en |
| dc.subject.keyword | 第二型糖尿病,胰島素阻抗性,SUV3,粒線體DNA,脂肪酸氧化, | zh_TW |
| dc.subject.keyword | Type 2 diabetes mellitus,insulin resistance,SUV3,mitochondrial DNA,fatty acid oxidation, | en |
| dc.relation.page | 59 | - |
| dc.identifier.doi | 10.6342/NTU202502261 | - |
| dc.rights.note | 未授權 | - |
| dc.date.accepted | 2025-07-25 | - |
| dc.contributor.author-college | 醫學院 | - |
| dc.contributor.author-dept | 分子醫學研究所 | - |
| dc.date.embargo-lift | N/A | - |
| 顯示於系所單位： | 分子醫學研究所 | |
文件中的檔案：
| 檔案 | 大小 | 格式 | |
|---|---|---|---|
| ntu-113-2.pdf 未授權公開取用 | 4.16 MB | Adobe PDF |
系統中的文件，除了特別指名其著作權條款之外，均受到著作權保護，並且保留所有的權利。