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系統識別號 U0026-0812200914272392
論文名稱(中文) 腦內投予胰島素對血糖恆定調控之研究
論文名稱(英文) Effect of central insulin on glucose homeostasis
校院名稱 成功大學
系所名稱(中) 藥理學研究所
系所名稱(英) Department of Pharmacology
學年度 96
學期 2
出版年 97
研究生(中文) 凌聖銘
研究生(英文) Sheng-Ming Ling
學號 s2695106
學位類別 碩士
語文別 中文
論文頁數 51頁
口試委員 指導教授-鄭瑞棠
口試委員-張文正
口試委員-許朝添
中文關鍵字 中樞  胰島素  副交感神經 
英文關鍵字 insulin  parasympathetic nerve  central 
學科別分類
中文摘要 胰島素在中樞負責調控血糖恆定及生殖激素的分泌,同時具有保護神經的功能。胰島素對長期血糖恆定主要透過迷走神經降低肝糖輸出。此外,胰島素是否能透過其他機轉,對葡萄糖代謝產生短期調控,目前仍不清楚。本研究發現,中樞給予胰島素能促進周邊胰島素釋放,且在一小時內達到降低血糖的效果。並且,中樞給予胰島素所產生的血中胰島素濃度增加及血糖下降,在迷走神經截斷或腹腔注射第三型蕈毒鹼受體阻斷劑後受到抑制。此說明迷走神經負責將中樞刺激傳至周邊,導致周邊的胰島素釋放和血糖下降的主要機轉。先前文獻指出,鉀離子通道的開啟是胰島素的中樞功能中,必須的訊息傳遞路徑。本研究中所發現的短期調控,在前處理磺醯尿素類降血糖藥物時受到抑制。針對磺醯尿素類降血糖藥物在中樞及周邊的功能性差異,利用動物模式,發現周邊給予磺醯尿素類降血糖藥物(sulphonylurea)能減弱中樞胰島素的食慾抑制效果。若長時間給予磺醯尿素類降血糖藥物能影響其短期血糖調控。綜上所述,經由鉀離子通道的開啟及迷走神經的活化,中樞給予胰島素透過促進周邊胰島素釋放,造成血糖下降。且周邊給予的磺醯尿素類降血糖藥物有可能對胰島素產生抑制作用。
英文摘要 Central administration of insulin has metabolic, reproductive and neurotrophic effects. The metabolic effects of insulin are responsible for controlling the long-term glucose homeostasis via an activation of parasympathetic nerves in peripheral, which results in reduction of hepatic glucose output. However, it is still unclear whether central insulin exerts the regulation of plasma glucose within short term. In this study, we found that central administration of insulin caused an increment of plasma insulin level and a counterpart decrement in plasma glucose level within one hour. These effects were blocked by vagotomy and intraperitoneal administration of 4-DAMP, a specific M3 antagonist, which points out the importance of vagus nerve in insulin release and plasma glucose lowering effect. KATP is a key mediator in central signaling pathway of insulin. We also found that plasma glucose-lowering effect was blocked by central administration of sulphonylurea, a KATP blocker. After investigation the opposing effect of sulphonylurea to central effect of insulin, we found that the anorexic effect of central insulin is abolished after peripheral administration of sulphonylurea. Administration of sulphonylurea for 7 days results in diminished plasma glucose-lowering effect of central insulin. In conclusion, central insulin decreased plasma glucose level by activation of vagus nerve, which resulted in release of insulin, and intraperitoneal administration of sulphonylurea interferes with central effect of insulin.
論文目次 中文摘要…………………………………………….IV
英文摘要…………………………………………….VI
縮寫表………………………………………………IX
第一章 緒論………………………………………1
第二章 實驗材料與方法………………………..7
第三章 實驗結果……………………………….13
第四章 討論……………………………………..17
第五章 結論………………………………………22
參考文獻…………………………………………..24
附圖…………………………………………………32
自述…………………………………………………51
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