Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/13330
標題: Oleic acid對大白鼠胰臟分泌胰島素之影響
Effects of Oleic Acid on Insulin Secretion in Perfused Rat Pancreas
作者: 吳采婷
Wu, Cia-Ting
關鍵字: insulin
胰島素
monounsaturated fatty acid
oleic acid
單元不飽和脂肪酸
油酸
出版社: 獸醫學系暨研究所
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摘要: 第2型糖尿病已經是一個全球的健康危機,並且有越來越嚴重的趨勢。研究指出,飲食攝取高量脂肪容易產生肥胖,目前有許多的研究致力於探討糖尿病與肥胖之間的機轉。更有動物實驗研究確立單元不飽和脂肪酸可能具有保護β胰臟細胞之功能。相對於飽和脂肪酸有害的影響,不飽和脂肪酸不但有益於改善這些現象,並且也可以避免胰臟β細胞受到飽和脂肪酸的傷害而造成的細胞凋亡(apoptosis)。本實驗即以活體灌流大白鼠胰臟之模式探討oleic acid對大白鼠胰臟分泌胰島素之影響。研究發現100μM之oleic acid-albumin可以直接刺激胰臟分泌胰島素,且會加強葡萄糖刺激胰島素分泌之作用。除此之外,oleic acid在50-150μM的濃度下,其刺激作用與劑量成正比。由1990年發現之核內接受器peroxisome proliferators-activated receptors (PPARs),其功能讓我們更了解脂肪酸與荷爾蒙代謝平衡和血糖調控的關係,早期的研究確定脂肪酸可以正向調控PPAR基因的轉錄作用,因此為了探討脂肪酸oleic acid對第2型糖尿病之作用機轉,我們利用PPAR-γ抑制劑LY294002和PPAR-α抑制劑MK886合併oleic acid灌流入大白鼠胰臟。實驗顯示MK886無法消除oleic acid所促使的胰島素釋放,而PI3K選擇性抑制劑LY294002則而可以抑制大部分之作用。由上述的實驗結果顯示oleic acid促使胰島素釋放的機制,可能主要是經由活化PPAR-γ的作用達到促使胰島素的釋放,因此PPAR-γ的訊息傳遞作用在維持基礎胰島素的釋放機制上扮演一個不容忽視的角色。
Type 2 diabetes is a worldwide health crisis and likely to get much worse. It was well known that intake of high-fat diet increased the risk of obesity. Much effort has been made to explore the role of obesity in the development of diabetes. Several studies have indicated that monounsaturated fatty acid may protected β cell function in animal model. In addition, contrary to the harmful effects of saturated fatty acid, unsaturated fatty acid with identical carbon chain length exhibits the opposite effects but also prevented β-cell from lipoapoptosis. In our studies, oleic acid-albumin was perfused into rat pancreas. We found that 100 μM oleic acid-albumin was able to stimulate insulin secretion and enhanced 10 mM glucose-induced insulin secretion. In addition, oleic acid(50-150 μM)stimulated insulin release in a dose-dependent manner. The discovery of the peroxisome proliferators-activated receptors (PPARs) in 1990 was the key to the understanding of peroxisome proliferation and improved our understanding in the function of adipocyte related to the homeostasis of blood glucose. Previous studies showed that fatty acid regulated gene transcription by increasing the activity of nucleus receptor, perpoxisome proliferators-activated receptor (PPAR). In order to understand the mechanisms of oleic acid effects on type 2 diabetes, we used PPAR-γ inhibitor(LY 294002, 3.9 μM) and PPAR-α inhibitor MK 886, 10μM) combined with oleic acid to perfuse rat pancreas. However, MK 886 did not decrease the stimulatory effect of oleic acid, whereas, LY 294002 inhibited the effects of oleic acid on insulin release. The results suggested that the mechanism of oleic acid-increased insulin secretion probably major mediated through the activation of PPAR-γ. However, the activation of PPAR-γ might play an important role in basal insulin secretion.
URI: http://hdl.handle.net/11455/13330
其他識別: U0005-0307200713142100
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