博碩士論文 91224013 詳細資訊




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姓名 陳晏航(Yen-Hung Chen)  查詢紙本館藏   畢業系所 生命科學系
論文名稱 第一型類胰島素生長因子、綠茶唲茶素及雌性素對3T3-L1脂肪細胞中resistin的基因表達有不同的調節效果
(Expression of resistin gene in 3T3-L1 adipocyte is differently regulated by IGF-I, EGCG, and estrogen)
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摘要(中) Resistin (Rstn) 這個新的脂肪細胞激素最近被分離出來,其功能會減少血糖耐受性,且進而造成嚴重的胰島素抗性。進一步的研究顯示Rstn的表達在遺傳以及飲食所造成的肥胖老鼠中會被誘導,而TZD之類用來治療糖尿病的藥物則可以抑制它的表達。基於這些觀察,Rstn被認為可能是介於糖尿病和肥胖之間的關鍵物質,並可以用來解釋TZD改良糖尿病的療效。根據過去的研究指出Rstn的表達量會受到許多影響胰島素敏感性的荷爾蒙與營養物質所調節。本篇研究的第一章則發現Rstn基因會受到第一型類胰島素生長因子藉由刺激某未知蛋白質的合成來抑制其表達。第二章的結果顯示綠茶中的唲茶素則經由加快Rstn mRNA的降解速度來抑制Rstn的表達。相反的,第三章的結果顯示雌性素則是會透過增加轉錄因子C/EBPα和Rstn啟動子的結合而促進Rstn的表達。故本論文的研究成果可以用來釐清第一型類胰島素生長因子、綠茶中的唲茶素及雌性素在胰島素抗性中所扮演的角色。
摘要(英) Recently, the novel adipocytokine resistin (Rstn) had been isolated. This protein hormone functions to impair glucose tolerance. In accordance with this view, Rstn induced severe insulin resistance. Furthermore, it was initially shown that Rstn was up-regulated in both genetic and diet-induced obesity in vivo and down-regulated by TZDs. On the basis of these observations, it had been postulated that Rstn might be both a link between obesity and diabetes, as well as a candidate to explain the anti-diabetic effects of TZDs. It had been clearly shown that Rstn mRNA expression was regulated by various hormones and nutrients which influence insulin sensitivity. In the chapter one of this study, we found that Rstn expression was reduced by insulin-like growth factor I (IGF-I) via an unknown protein synthesis. Chapter two showed that EGCG, the major green tea polyphenol, suppressed Rstn expression through accelerating Rstn mRNA degradation. Contrarily, chapter three showed that estrogen could induce Rstn expression significantly via increasing the association of transcription factor C/EBPα with Rstn promoter. These results might help clarify the roles of IGF-I, EGCG, and estrogen playing in insulin resistance.
關鍵字(中) ★ 第一型類胰島素生長因子
★ 抗素
★ 雌性素
★ 綠茶唲茶素
★ 肥胖
★ 糖尿病
關鍵字(英) ★ obesity
★ Estrogen
★ IGF-I
★ EGCG
★ resistin
★ diabetes
論文目次 Abstract III
中文摘要 IV
Acknowledgements V
List of figures VIII
Abbreviations X
Chapter one Differential regulation of resistin gene expression and protein secretion by insulin-like growth factor I
Abstract 1
Introduction 2
Materials and Methods 5
Results 12
Discussion 17
References 20
Chapter two Modulation of resistin gene expression by green tea epigallocatechin gallate
Abstract 27
Introduction 28
Materials and Methods 31
Results 36
Discussion 40
References 45
Chapter three Up-regulation of resistin gene expression in 3T3-L1 adipocytes by estrogen
Abstract 51
Introduction 53
Materials and Methods 56
Results 63
Discussion 70
References 74
General conclusions 82
Table 1 113
Appendix 114
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Chapter 2
1. Steppan CM, Bailey ST, Bhat S 2001 The hormone resistin links obesity to diabetes. Nature 409:307-312
2. Kim KH, Lee K, Moon YS, Sul HS 2001 A cysteine-rich adipose tissue-specific secretory factor inhibits adipocyte differentiation. J Biol Chem 276:11252-11256
3. Ghosh SG, Singh AK, Aruna B, Mukhopadhyay S, Ehtesham NZ 2003 The genomic organization of mouse resistin reveals major differences from the human resistin: functional implications. Gene 305:27-34
4. Steppan CM, Brown EJ, Wright CM 2001 A family of tissue-specific resistin-like molecules. Proc Natl Acad Sci USA 98:502-506
5. Banerjee RR, Rangwala SM, Shapiro JS 2004 Regulation of fasted blood glucose by resistin. Science 303:1195-1198
6. Moon B, Kwan JJ, Duddy N, Sweeney G, Begum N 2003 Resistin inhibits glucose uptake in L6 cells independently of changes in insulin signaling and GLUT4 translocation. Am J Physiol Endocrinol Metab 285:E106-115 (Epub 2003 Mar 04)
7. Verma S, Li SH, Wang CH, Fedak PWM, Li RK, Weisel RD, Mickle DAG 2003 Resistin promotes endothelial cell activation further evidence of adipokine-endothelial interaction. Circulation 108:736-740
8. Degawa-Yamauchi M, Bovenkerk J, Juliar BE 2003 Serum resistin (FIZZ3) protein is increased in obese humans. J Clin Endocrinol Metab 88:5452-5455
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42. Seo JB, Noh MJ, Yoo EJ 2003 Functional characterization of the human resistin promoter with adipocyte determination-and differentiation-dependent factor 1/sterol regulatory element binding protein 1c and CCAAT enhancer binding protein-α. Mol Endocrinol 17:1522-1533
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Chapter 3
1. Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA 2001 The hormone resistin links obesity to diabetes. Nature 409:307-312
2. Ukkola O 2002 Resistin—a mediator of obesity-associated insulin resistance or an innocent bystander? Eur J Endocrinol 147:571–574
3. Steppan CM, Lazar MA 2002 Resistin and obesity-associated insulin resistance. Trends Endocrinol Metab 13:18–23
4. Hotamisligil GS 2003 The irresistible biology of resistin. J Clin Invest 111:173–174
5. Rajala MW, Obici S, Scherer PE, Rossetti L 2003 Adipose-derived resistin and gut-derived resistin-like molecule-beta selectively impair insulin action on glucose production. J Clin Invest 111:225–230
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指導教授 高永旭(Yung-Hsi Kao) 審核日期 2004-7-8
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