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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 葉秀慧(Shiou-Hwei Yeh) | |
| dc.contributor.author | Yi-Chun Lu | en |
| dc.contributor.author | 盧怡君 | zh_TW |
| dc.date.accessioned | 2021-06-08T03:58:20Z | - |
| dc.date.copyright | 2018-09-04 | |
| dc.date.issued | 2018 | |
| dc.date.submitted | 2018-08-13 | |
| dc.identifier.citation | 1. Freiss, G. and D. Chalbos, PTPN13/PTPL1: An Important Regulator of Tumor Aggressiveness. Anti-Cancer Agents in Medicinal Chemistry, 2011. 11(1): p. 78-88.
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/22021 | - |
| dc.description.abstract | FAP-1 (Fas-associated phosphotase-1) 是一個非受器型的蛋白質酪胺酸去磷酸酶，在許多腫瘤中的表現量較低，因而被認為可能是腫瘤抑制基因。FAP-1 大多的功能是在細胞實驗中驗證，而在生理及病理上實際的功能仍尚待以動物實驗證實。在本篇論文中，我們將利用來自Dr. Hendriks 實驗室的FAP-1 phosphatase-deficient (FAP-1△P/△P) 小鼠作為動物實驗模型，來探討FAP-1 的生理功能。有趣的是，我們發現在C57BL/6J的基因背景下，FAP-1△P/△P 小鼠有肥胖的表現型產生，利用MRI全身體組成分析後，FAP-1△P/△P小鼠具有較高的脂肪含量比例，將小鼠犧牲後取得的脂肪重量也得到較重的結果。脂肪過量的原因可能是由過度的飲食或是過多的脂肪生合成反應造成，因此我們首先檢視進食、進水量，結果指出FAP-1△P/△P小鼠並無攝食較多的行為。再以組織切片染色檢視肝臟及白色脂肪組織的細胞型態，脂肪組織有脂肪細胞肥大的表型產生，但並無過多的脂肪堆積在肝臟內形成脂肪肝。血液分析顯示FAP-1△P/△P小鼠在禁食時有較高的血糖值、胰島素濃度及HOMA-IR數值，即FAP-1△P/△P小鼠有胰島素抗性(insulin resistance) 的表型，再以管餵葡萄糖耐受性實驗(OGTT)及胰島素耐受性實驗(ITT)得到證實。丙酮酸耐受性實驗(pyruvate tolerance test)結果則指出FAP-1△P/△P小鼠並無較旺盛的糖質新生。然而，小鼠正子斷層掃描實驗 (Positron emission tomography, PET)顯示FAP-1△P/△P小鼠的腦部有較差的葡萄糖吸收。本篇論文的研究指出，FAP-1△P/△P小鼠較高的禁食血糖值及胰島素抗性可能是由於腦部對於葡萄糖的不吸收所導致。未來的研究將著重於FAP-1是透過何種機制來調控腦部吸收葡萄糖，進而避免胰島素抗性產生。 | zh_TW |
| dc.description.abstract | FAP-1 (Fas-associated phosphotase-1), a non-receptor protein tyrosine
phosphatase, was found decreased in several tumors and thus suggested a putative tumor suppressor gene. Though a variety of FAP-1 functions were revealed by cell culture-based assay, the physiological and pathological function of FAP-1 is still remained unclear and need to be validated in vivo. The current study proposed to investigate the FAP-1 function by using the FAP-1 phosphatase-deficient (FAP-1△P/△P)mouse model, which was established and delivered from Dr. Hendriks lab. Interestingly, we found an overweight/obese phenotype of FAP-1△P/△P mice with the B6J genetic background, which were mainly contributed by an increased body fat composition. FAP-1△P/△P mice have hypertrophic adipocytes but no fatty liver. Blood examination revealed an elevation of fasting glucose and insulin concentration, and also a significantly higher HOMA-IR index in FAP-1△P/△P mice. It thus suggested an insulin resistance phenotype in FAP-1△P/△P mice, which had been further confirmed by oral glucose tolerance test (OGTT) and insulin tolerance test (ITT). Further pyruvate tolerance test (PTT) did not show elevated hepatic gluconeogenesis; instead an impaired glucose uptake in the brain of FAP-1△P/△P mice was identified by the positron emission tomography (PET) test. The results suggested that the higher blood glucose and insulin resistance phenotypes in the FAP-1△P/△P mice could be caused by impaired glucose uptake in brain. This possibility and the underlying mechanism for FAP-1 functions in regulating the glucose uptake in brain to avoid insulin resistance mice is the next issue to be addressed. | en |
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| dc.description.tableofcontents | 致謝…………………………………………………………………………………....I
中文摘要……………………………………………………………………….…….II 英文摘要…………………………………………………………………………….III 目錄…………………………………………………………………………………..IV 序論……………………………………………………………………………………1 一、Fas-associated phosphatsse-1 (FAP-1)基因之蛋白質結構與特性………...1 二、脂肪的生合成………………………………………………..……………..2 三、葡萄糖的代謝調控………………………………………………...….……3 四、胰島素抗性…………………………………………………………………4 五、葡萄糖在腦中的代謝………………………………………………………5 研究目的………………………………………………………………………………7 材料與方法……………………………………………………………………………8 一、實驗動物……………………………………………………………………8 二、抗體……………………………………………………………………..…..8 三、小鼠組織之蛋白質萃取………………………………………..………..…9 四、蛋白質定量分析…………………………………………………..……..…9 五、SDS-PAGE 蛋白質膠體電泳……………………………….…………..…9 六、西方墨點法…………………………………………………………..…..…9 七、RNA 萃取與反轉錄定量聚合酶連鎖反應…………….………...………10 八、小鼠耐受性實驗………………………………………………………..…11 九、小鼠全身體組成分析…………………………………………..…………11 十、小鼠正子斷層掃描……………………………………………..…………11 十一、小鼠進食、進水量測試……………………………..…………………11 研究結果………………………………………………………………………..……12 一、FAP-1△P/△P小鼠有體重較重的表型產生…………………………………12 二、FAP-1△P/△P小鼠有較多的脂肪組織………………………………………12 三、FAP-1△P/△P 小鼠無進食、進水量的差異……………………………….…12 四、FAP-1△P/△P 小鼠有脂肪細胞肥大的表型…………………………..……12 五、FAP-1△P/△P 小鼠的血液檢查顯示高血糖及胰島素抗性的表型…..….…13 六、葡萄糖、胰島素及丙酮酸耐受性實驗顯示FAP-1△P/△P 小鼠有較WT 小鼠 差的葡萄糖吸收及胰島素敏感性……………………………………..…13 七、正子斷層掃描實驗顯示FAP-1△P/△P 小鼠在禁食後的腦部有較WT 小鼠 差的葡萄糖吸收………………………………………………………..…14 八、AP-1△P/△P 小鼠在禁食後腦部的葡萄糖載體蛋白3 (glucose transporter 3, GLUT3) 表現量較WT 小鼠低，非禁食時則較高…………..…………15 結果討論……………………………………………………………..………………16 小鼠基因型背景、腸道菌叢與FAP-1 交互作用的可能性…………….…………16 FAP-1 在神經修復中可能的角色……………………………………………..……16 FAP-1 可能為第三型糖尿病的調控因子…………………………………….……17 FAP-1 調控GLUT3 表現量的可能路徑……………………………………………17 在禁食及非禁食情況下，FAP-1 調控GLUT3 表現量的可能路徑………………18 圖附錄………………………………………………………………………………..19 圖一、FAP-1△P/△P 小鼠有體重較重的表型產生……………………………..…….19 圖二、FAP-1△P/△P 小鼠體重較WT 小鼠重且脂肪較多…………………………...20 圖三、FAP-1△P/△P 小鼠有脂肪細胞肥大的表型…………………………..………22 圖四、FAP-1△P/△P 小鼠無進食、進水量的差異……………………………………23 圖五、FAP-1△P/△P 小鼠無脂肪肝的表型……………………………………………24 圖六、FAP-1△P/△P 小鼠血中三酸甘油脂及總膽固醇值較WT 沒有顯著差異，但有 較高的血糖及胰島素抗性…………………………………………………………..25 圖七、葡萄糖耐受性實驗顯示FAP-1△P/△P 小鼠有較WT 差的葡萄糖吸收….…27 圖八、胰島素耐受性實驗顯示FAP-1△P/△P 小鼠有較WT 差的胰島素敏感性….28 圖九、丙酮酸耐受性實驗顯示FAP-1△P/△P 小鼠之肝臟糖質新生與WT 無顯著差 異………………………………………………………………………………….….29 圖十、正子斷層掃描實驗顯示FAP-1△P/△P 小鼠在禁食後的腦部有較WT 小鼠差的 葡萄糖吸收…………………………………………………………………….…….30 圖十一、正子斷層掃描實驗顯示FAP-1△P/△P 小鼠在禁食後的腦部有較WT 小鼠差 的葡萄糖吸收，在非禁食時則有較好的葡萄糖吸收…………………..…………..31 圖十二、 FAP-1△P/△P 小鼠在禁食後的葡萄糖載體蛋白3(glucose transporter 3, GLUT3)表現量較WT小鼠低，非禁食時則較高…………………………………...32 圖十三、在禁食時，FAP-1 調控 GLUT3 蛋白質及mRNA 表現量可能的路徑 圖……………………………………………………………………………………..33 參考文獻………………………………………………………………………..……34 | |
| dc.language.iso | zh-TW | |
| dc.subject | 葡萄糖吸收 | zh_TW |
| dc.subject | FAP-1 | zh_TW |
| dc.subject | 肥胖 | zh_TW |
| dc.subject | 脂肪細胞肥大 | zh_TW |
| dc.subject | 胰島素抗性 | zh_TW |
| dc.subject | insulin resistance | en |
| dc.subject | glucose uptake | en |
| dc.subject | FAP-1 | en |
| dc.subject | overweight | en |
| dc.subject | hypertrophic adipocytes | en |
| dc.title | FAP-1 基因調控葡萄糖代謝之功能研究 | zh_TW |
| dc.title | A potential function of FAP-1 gene in regulating the glucose metabolism | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 106-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 陳培哲(Pei-Jer Chen),周祖述(Tzuu-Shuh Jou),黃怡萱(Yi-Shuian Huang) | |
| dc.subject.keyword | FAP-1,肥胖,脂肪細胞肥大,胰島素抗性,葡萄糖吸收, | zh_TW |
| dc.subject.keyword | FAP-1,overweight,hypertrophic adipocytes,insulin resistance,glucose uptake, | en |
| dc.relation.page | 41 | |
| dc.identifier.doi | 10.6342/NTU201802616 | |
| dc.rights.note | 未授權 | |
| dc.date.accepted | 2018-08-13 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 微生物學研究所 | zh_TW |
| 顯示於系所單位： | 微生物學科所 | |
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