發(fā)布時(shí)間：2018-04-24 23:14

  本文選題：胃旁路手術(shù) + 法尼酯X受體��； 參考：《深圳大學(xué)》2017年碩士論文

【摘要】：胰島B細(xì)胞分泌的胰島素是機(jī)體降低血糖的唯一激素,胰島B細(xì)胞功能障礙所致的胰島素水平降低直接導(dǎo)致糖尿病的發(fā)生發(fā)展。B細(xì)胞分泌胰島素是一個(gè)精確而復(fù)雜的調(diào)控過程,葡萄糖是體內(nèi)促進(jìn)胰島素分泌的主要因素,它通過胰島B細(xì)胞膜轉(zhuǎn)運(yùn)體GLUT2轉(zhuǎn)入細(xì)胞,在線粒體代謝產(chǎn)生ATP,提高胞漿ATP/ADP比值,關(guān)閉細(xì)胞膜ATP敏感的鉀通道(KATP通道),導(dǎo)致細(xì)胞內(nèi)帶正電荷的鉀離子增多,細(xì)胞膜去極化,開發(fā)電壓門控鈣通道,鈣離子內(nèi)流使細(xì)胞內(nèi)鈣離子濃度升高,誘發(fā)胰島素囊泡的出胞。臨床和基礎(chǔ)研究發(fā)現(xiàn)胃旁路手術(shù)(RYGB)能顯著糾正2型糖尿病高血糖癥狀,其效應(yīng)與增加胰島素分泌相關(guān)。我們課題組的前期工作發(fā)現(xiàn)RYGB增加胰島素分泌的同時(shí),伴有胰島B細(xì)胞法尼酯X受體(Farnesoid X receptor,FXR)的升高。FXR是膽汁酸受體。作為核受體,FXR在糖脂代謝的調(diào)解中發(fā)揮重要作用。本論文利用全細(xì)胞電生理技術(shù),在胰島B細(xì)胞中記錄了葡萄糖誘發(fā)的動(dòng)作電位和膜電位,且研究了胰島B細(xì)胞上鈣電流的大小。利用Q-PCR檢測和western blot等技術(shù)檢測了胰島中鈣通道和TRPA1通道在mRNA和蛋白質(zhì)水平的表達(dá)。利用ELASA技術(shù)檢測了INS-1E細(xì)胞系和小鼠胰島在葡萄糖刺激下的胰島素分泌能力。通過以上這些實(shí)驗(yàn)技術(shù),我們主要得到了以下研究結(jié)果:(1)FXR通過增進(jìn)胰島B細(xì)胞TRPA1的表達(dá),提高B細(xì)胞對(duì)葡萄糖刺激的敏感性,繼而增進(jìn)糖刺激的胰島素分泌;(2)FXR通過增進(jìn)胰島B細(xì)胞L-型鈣通道轉(zhuǎn)錄水平,提高B細(xì)胞鈣通道的表達(dá),增大糖刺激所致的鈣電流,導(dǎo)致胰島素分泌增大。以上結(jié)果闡明RYGB增進(jìn)胰島素分泌的機(jī)制,為臨床治療糖尿病提供新的科學(xué)依據(jù)及新的治療靶點(diǎn)。
[Abstract]:Insulin secreted by islet B cells is the only hormone that reduces blood glucose. The decrease of insulin level caused by islet B cell dysfunction directly leads to the occurrence and development of diabetes. B cells secrete insulin is a precise and complex regulatory process. Glucose is the main factor that promotes insulin secretion in vivo. It is transferred into cells through islet B cell membrane transporter GLUT2, which produces ATP in mitochondria metabolism and enhances the ratio of cytoplasmic ATP/ADP. Closing the K + channel sensitive to ATP leads to the increase of positively charged potassium ions in the cell membrane, depolarization of cell membrane, development of voltage-gated calcium channel, and the increase of intracellular calcium ion concentration by calcium ion influx, which induces the release of insulin vesicle. Clinical and basic studies showed that RYGBcan significantly correct hyperglycemia in type 2 diabetes mellitus, and its effect is related to the increase of insulin secretion. Our previous work found that RYGB increased insulin secretion accompanied by the increase of Farnesoid X receptor FXR. FXR was a bile acid receptor. As a nuclear receptor, FXR plays an important role in the regulation of glucose and lipid metabolism. In this paper, the action potential and membrane potential induced by glucose in islet B cells were recorded by whole-cell electrophysiological technique, and the magnitude of calcium current on islet B cells was studied. The expression of calcium channel and TRPA1 channel in pancreatic islets at the level of mRNA and protein were detected by Q-PCR detection and western blot techniques. The insulin secretion ability of INS-1E cell line and islet of mice stimulated by glucose was detected by ELASA technique. Through these experimental techniques, we have obtained the following results: 1. FXR enhances the sensitivity of B cells to glucose stimulation by enhancing the expression of TRPA1 in islet B cells. The insulin secretion induced by glucose stimulation was increased by increasing the transcription level of L- type calcium channel, increasing the expression of calcium channel and increasing the calcium current induced by glucose stimulation, which led to the increase of insulin secretion. These results indicate that RYGB enhances insulin secretion and provides a new scientific basis and new therapeutic target for the clinical treatment of diabetes mellitus.
【學(xué)位授予單位】：深圳大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R587.1

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 Kohzo Takebayashi;Yoshimasa Aso;Toshihiko Inukai;;Role of bile acid sequestrants in the treatment of type 2 diabetes[J];World Journal of Diabetes;2010年05期

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本文編號(hào)：1798688