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研究生:張立煒
研究生(外文):Li-Wei Chang
論文名稱:內皮素-1對大白鼠脂肪細胞上脂肪分解作用之影響
論文名稱(外文):Effects of Endothelin-1 on Lipolysis in Rat Adipocytes
指導教授:何橈通何橈通引用關係
指導教授(外文):Lo-Tone Ho
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:生理學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2004
畢業學年度:92
語文別:中文
論文頁數:64
中文關鍵詞:內皮素-1脂解作用胰島素阻抗腺苷酸環化酶
外文關鍵詞:ET-1lipolysisinsulin resistancecAMP
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  • 下載下載:32
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內皮素-1為一強力血管收縮物質,除了在於心血管疾病外,還扮演著其他重要的角色。臨床研究指出在胰島素阻抗患者身上其體內內皮素-1濃度增高之外,血糖增加或是高胰島素血症等皆伴隨另一種症狀即高血脂症產生。吾等因此假設內皮素-1會透過特定的訊息傳遞途徑影響到體內脂質代謝。為探討此問題,我們利用離體的雄性大白鼠副睪脂肪細胞來進行研究,先以不同濃度之異丙基腎上腺素(10-6 M~ 10-10 M)或以胰島素(10-9 M~10-12 M)處理脂肪細胞,得到異丙基腎上腺素促進脂肪分解和胰島素抗異丙基腎上腺素脂解能力得到之一個劑量效應圖。接著利用不同濃度之內皮素-1處理脂肪細胞觀察其對於脂肪分解的影響,以及其對異丙基腎上腺素促脂解及胰島素抗脂解作用的共同效應為何,並施予BQ610 (10-6 M)、BQ788 (10-6 M) (內皮素選擇性拮抗劑)來探究內皮素-1處理脂肪細胞對於脂肪細胞代謝途徑的作用方式為透過何種內皮素受體來達成。並利用腺苷酸環化酶(adenylate cyclase)抑制劑觀察cAMP在內皮素-1影響在脂肪分解的訊息途徑為何。結果顯示(一)內皮素-1會促進脂肪的分解,且此作用乃是透過內皮素A型接受體(ETA);(二)內皮素-1會促進脂肪分解與cAMP或腺苷酸環化酶無關;(三)內皮素-1所誘發的脂解會受到胰島素的抑制; (四)內皮素-1會抑制異腎上腺素所誘發的脂解。
Endothelin-1 (ET-1) was originally suggested to be a potent vasoconstrictive peptide, and further investigations demonstrated that ET-1 may play an important role in the pathology of cardiovascular diseases. Clinical studies revealed that in addition to hyperglycemia, impaired glucose tolerance, and hyperendothelinemia, dyslipidemia is a common characteristic in patients with type 2 diabetes. I performed experiments to test the hypothesis that ET-1 may directly or indirectly interfere with lipid metabolism through an unknown signaling. Adipocytes isolated from the epidydimal fat pads of male Sprague Dawley rats were used to study the lipolytic effect of isoproterenol (10-6 M~10-10 M) and antilipolytic effect of insulin (10-9 M~10-12 M). The influence of ET-1 alone or in combination with isoproterenol or insulin on lipolysis was also investigated. Treatment of BQ610 (10-6 M) and BQ788 (10-6 M), selective antagonist for ET-1 A receptor and B receptor, respectively, was conducted to analyze what type of ET receptor was involved in the ET-1-mediated lipolytic effect. Additionally, an adenylate cyclase inhibitor was used to observe the role of cAMP in the in the ET-1- mediated lipolytic effect. My data indicated that: (a) ET-1 stimulated lipolysis via ET type A receptor, and the ET-1–induced lipolytic effect did not involve cAMP and adenylate cyclase; (b) the ET-1-induced lipolysis was inhibited by insulin; and (c) ET-1 also suppressed the lipolysis stimulated by isoproterenol. Conclusively, these findings suggested that ET-1 may serve a dual role in the regulation of lipolysis in rat adipocytes.
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