臺灣博碩士論文加值系統

　　本實驗的目的為探討血清素對胰島素阻抗的影響，而使用選擇性血清素吸回抑制劑(SSRI)來評估其對胰島素抗阻性的改善效果及可能的機制。由HOMA-IR的實驗發現，在果糖誘發胰島素抗性的大白鼠身上，長期投予fluoxetine及paroxetine，可改善胰島素的抗阻性，同時，可以促進骨骼肌的葡萄糖吸入。在離體骨骼肌直接以5-HT刺激，也能夠以劑量相關性的方式促進葡萄糖的吸入；顯示SSRI能夠藉由5-HT來促進骨骼肌的葡萄糖吸入作用而改善胰島素抗阻性。文獻指出，在大白鼠的骨骼肌具有5-HT2受體的分布，因此，利用5-HT2受體拮抗劑ketanserin 探討5-HT2受體在SSRI改善胰島素抗性的角色。本研究看到，ketanserin 可以阻擋fluoxetine及paroxetine 改善胰島素抗阻的作用，也能夠以劑量相關性的方式阻擋5-HT在離體骨骼肌促進的葡萄糖吸入作用。另外，5-HT2受體作用劑DOI，也能夠改善果糖老鼠的胰島素抗性，促進離體骨骼肌的葡萄糖吸入。由以上可知，SSRI可以經由5-HT2受體促進骨骼肌的葡萄糖吸入作用來改善胰島素抗阻性，顯示5-HT2受體在改善胰島素抗阻性上扮演一個重要的角色。

　In the present study, the effect of selective serotonin reuptake inhibitors (SSRIs) on insulin resistance was investigated. Chronic administration of fluoxetine and paroxetine could improve insulin resistance in fructose-fed rats by homeostasis model assessment-insulin resistance (HOMA-IR), and increase glucose uptake of skeletal muscle. 5-HT could directly stimulate glucose uptake of isolated skeletal muscle in a dose-dependent manner. The results indicate SSRIs could improve insulin resistance through increasing glucose uptake of skeletal muscle. Other study has report that there was the expression of 5-HT2 receptor in rat skeletal muscle. Therefore, the role of 5-HT2 receptor in improvement of insulin resistance by SSRIs was also investigated by using 5-HT2 antagonist, ketanserin. Experiments observed ketanserin could inhibit the effect of fluoxetine and paroxetine on improvement of insulin resistance. Ketanserin dose-dependently suppressed the stimulatory effect of 5-HT on glucose uptake of skeletal muscle. Besides,
5-HT2 agonist, DOI improved insulin resistance in fructose-fed rats, as well as dose-dependently increased glucose uptake of skeletal muscle. The present results indicate that SSRIs can improve insulin resistance by stimulating glucose uptake in skeletal muscle via 5-HT2 receptor. Thus, 5-HT2 receptor had an important role in the improvement of insulin resistance.

目錄

縮寫表　　　　　　　　　　　　　　　　　　　　1
第一章　緒論　　　　　　　　　　　　　　　　　2
第二章　方法及材料　　　　　　　　　　　　　　7
第三章　實驗結果　　　　　　　　　　　　　　　19
第四章　討論　　　　　　　　　　　　　　　　　31
第五章　結論　　　　　　　　　　　　　　　　　37
參考文獻　　　　　　　　　　　　　　　　　　　39
附圖　　　　　　　　　　　　　　　　　　　　　47
自述　　　　　　　　　　　　　　　　　　　　　67

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