請用此 Handle URI 來引用此文件：
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/80343完整後設資料紀錄
| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 張以承(Yi-Cheng Chang) | |
| dc.contributor.author | Yu-Ju Liu | en |
| dc.contributor.author | 劉育如 | zh_TW |
| dc.date.accessioned | 2022-11-24T03:04:48Z | - |
| dc.date.available | 2021-08-31 | |
| dc.date.available | 2022-11-24T03:04:48Z | - |
| dc.date.copyright | 2021-08-31 | |
| dc.date.issued | 2021 | |
| dc.date.submitted | 2021-08-17 | |
| dc.identifier.citation | 1 Nkhoma, E. T., Poole, C., Vannappagari, V., Hall, S. A. Beutler, E. The global prevalence of glucose-6-phosphate dehydrogenase deficiency: a systematic review and meta-analysis. Blood Cells Mol Dis 42, 267-278, 2009. 2. Rosalind E Howes.et al.Spatial distribution of G6PD deficiency variants across malaria-endemic regions.Malaria Journal 12:418, 2013. 3 Cappellini, M. D. Fiorelli, G. Glucose-6-phosphate dehydrogenase deficiency. Lancet 371, 64-74, 2008. 4 Beutler, E. The genetics of glucose-6-phosphate dehydrogenase deficiency.Semin Hematol 27, 137-164, 1990. 5 Huang, C. S. et al. Neonatal jaundice and molecular mutations in glucose-6- hosphate dehydrogenase deficient newborn infants. Am J Hematol51, 19-25, 1996 6 Chiang, S. H., Wu, S. J., Wu, K. F. Hsiao, K. J. Neonatal screening for glucose- -phosphate dehydrogenase deficiency in Taiwan. Southeast Asian J Trop Med Public Health 30 Suppl 2, 72-74, 1999. 7 McCurdy, P. R., Kirkman, H. N., Naiman, J. L., Jim, R. T. Pickard, B. M. A Chinese variant of glucose-6-phosphate dehydrogenase. J Lab Clin Med 67,374-385, 1966. 8. Hwang S, Mruk K, Rahighi S, Raub AG,, Chen CH, Dorn LE, Horikoshi N, Wakatsuki S, Chen JK, Mochly-Rosen D. Correcting glucose-6-phosphate dehydrogenase deficiency with a small-molecule activator.Nat Communication. 9:4045, 2018 9 Lai YK, et al.Glucose-6-phosphate dehydrogenase deficiency and risk oh diabetes: a systematic review and meta-analysis. Ann Hematol. 96:839-845, 2017. 10 Robert C. Stanton. et al.Glucose-6-phosphate dehydrogenase-deficient mice have increased renal oxidative stress and increased albuminuria. The FASEB Journal 24(2):609-616, 2018. 11 VujkovicM,et al.Discovery of 318 new risk loci for type 2 diabetes and related vascular outcomes among 1.4 million participants in a multi-ancestry meta-analysis. Nature Genetics 52:6800, 2020. 12 James K. Chen,DariaMochly-Rosen.Correcting glucose-6-phosphate dehydrogenase deficiency with a small-molecule activator. Nature Communication 9:4045, 2018. 13 Jose Vin ̃a, Manuel Serrano.G6PD protects from oxidative damage and improves health span in mice. Nature Communications,7:10894, 2016. 14 Chul-Ho Lee,Jae Bum Kim.Glucose-6-Phosphate Dehydrogenase Deficiency Improves Insulin Resistance With Reduced Adipose Tissue Inflammation in Obesity. Diabetes 65(9):2624-38, 2016. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/80343 | - |
| dc.description.abstract | "在全球約有4 億人有glucose-6-phosphate dehydrogenase (G6PD)基因變異，G6PD 突變是世界第二的常見單基因突變。位置在Ｘ染色體遠端長臂的一組基因座(Xq28）。缺乏G6PD 使細胞無法產出足夠的nicotinamide adenine dinucleotide phosphate(NADPH)，伴隨reduced glutathione (GSH)降低，使氧化壓力增加。紅血球方面G6PD 的缺乏很容易氧化造成溶血。在台灣，估計大約有1.61%（男生2.81%，女生0.70%）人口帶有G6PD 基因突變, 其中以c.1376G>T(p.R459L)的點突變(廣東型蠶豆症）最常見。 在一篇統合型研究中中，G6PD 缺乏可能會導致罹患糖尿病風險增加。大規模的第二型糖尿病基因掃描也發現G6PD 基因變異會引起糖尿病，因此我們以小鼠模型驗證，發現相對於人類只有一個G6PD 基因, 小鼠有兩個同源G6PD 基因，一條在X 性染色體及另一條在第5 條染色體上的G6pd2。為模擬台灣常見廣東型蠶豆症，本實驗使用CRISPR-Cas9 系統在G6pdx 中產生G>T 的點突變及在小鼠第二條染色體剔除G6pd2，產生G6PD 雙突變的小鼠。 我們發現G6PD 雙突變小鼠餵食高脂高蔗糖飼料相對於對照組小鼠，體重上升，胰島素阻抗性增加、葡萄糖耐受性減少、脂肪肝增加、並可能產生血脂異常與腎功能異常，伴隨脂肪細胞肥大。藉由血液抹片與血球計數發現並非溶血造成、我們探討G6PD 雙突變的老鼠肥胖原因，發現其能量消耗減少為主要原因。" | zh_TW |
| dc.description.provenance | Made available in DSpace on 2022-11-24T03:04:48Z (GMT). No. of bitstreams: 1 U0001-2006202119102100.pdf: 9456129 bytes, checksum: bf8676fbb95eede04838941c0f433610 (MD5) Previous issue date: 2021 | en |
| dc.description.tableofcontents | "口試論文審書 ii 致謝 iii 中文摘要 iv 英文摘要 v 第一章研究背景與動機 2 1 前言 2 2 背景介紹 3 3在台灣方面 5 第二章研究方法 8 2.1動物飼育 8 2.2廣東型蠶豆症嵌入鼠G6PD2-/-G6PDXCANTON的製作 8 2.3 利用PCR 檢定基因 9 2.4廣東型蠶豆症嵌入鼠餵食高脂飼料會表現肥胖型症狀 9 2.5評估G6PD2-/-G6PDXCANTON小鼠之葡萄不耐受性及胰島素阻抗性 9 2.6測量廣東型蠶豆症嵌入鼠之食物攝入量與能量消耗量 10 2.7廣東型蠶豆症嵌入鼠犧牲採樣取組織 10 2.8蘇木素-伊紅染色(H E染色) 10 2.9廣東型蠶豆症嵌入鼠做血液抹片 11 2.10 統計分析 11 第三章結果 12 1. 廣東型蠶豆症嵌入鼠G6PD2-/-G6PDXCANTON的製作 12 2. 廣東型蠶豆症嵌入鼠餵食高脂飼料會表現肥胖型症狀 12 3.廣東型蠶豆症嵌入鼠表現胰島素阻抗及葡萄糖不耐受性 12 4. 廣東型蠶豆症嵌入鼠在餵食高脂高蔗糖飼料時, 能量消耗比起野生型降低 13 第四章討論 14 圖 17 表 23 第五章參考文獻 25" | |
| dc.language.iso | zh-TW | |
| dc.subject | 脂肪肝 | zh_TW |
| dc.subject | 6-磷酸葡萄糖脫氫酶缺乏症 | zh_TW |
| dc.subject | 氧化壓力 | zh_TW |
| dc.subject | 胰島素阻抗性 | zh_TW |
| dc.subject | 葡萄糖耐受性 | zh_TW |
| dc.subject | 肥胖 | zh_TW |
| dc.subject | fatty liver | en |
| dc.subject | glucose intolerance | en |
| dc.subject | 6-phosphate glucose dehydrogenase deficiency | en |
| dc.subject | obesity | en |
| dc.subject | insulin resistance | en |
| dc.subject | oxidative stress | en |
| dc.title | 廣東型 G6PD 突變的小鼠產生肥胖、胰島素阻抗性、葡萄糖耐受不良與脂肪肝 | zh_TW |
| dc.title | "Mice carrying G6PD Canton mutation develop obesity, insulin resistance, glucose intolerance, and fatty liver" | en |
| dc.date.schoolyear | 109-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 莊立民(Hsin-Tsai Liu),李妮鍾(Chih-Yang Tseng) | |
| dc.subject.keyword | 6-磷酸葡萄糖脫氫酶缺乏症,氧化壓力,胰島素阻抗性,肥胖,葡萄糖耐受性,脂肪肝, | zh_TW |
| dc.subject.keyword | 6-phosphate glucose dehydrogenase deficiency,oxidative stress,obesity,insulin resistance,glucose intolerance,fatty liver, | en |
| dc.relation.page | 26 | |
| dc.identifier.doi | 10.6342/NTU202101067 | |
| dc.rights.note | 同意授權(限校園內公開) | |
| dc.date.accepted | 2021-08-17 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 分子醫學研究所 | zh_TW |
| 顯示於系所單位： | 分子醫學研究所 | |
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