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。 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.
