American ginseng stimulates insulin production and prevents apoptosis through regulation of uncoupling protein-2 in cultured beta cells.
American ginseng stimulates insulin production and prevents apoptosis through regulation of uncoupling protein-2 in cultured beta cells.
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DOI：
10.1093/ecam/nel026
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发表时间：
2006-09
期刊：
影响因子：
--
通讯作者：
Luo L
中科院分区：
文献类型：
--
作者：
Luo JZ;Luo L
西洋参根在实验和临床上都显示出实现葡萄糖稳态的能力，但人参用于实现其对糖尿病的治疗效果的未知机制限制了其应用。胰腺β细胞的胰岛素分泌中断被认为是糖尿病的主要原因。已发现线粒体蛋白解偶联蛋白-2（UCP-2）在胰岛素合成和β细胞存活中起关键作用。我们的初步研究发现，西洋参提取物抑制UCP-2的表达，这可能有助于人参保护β细胞死亡和改善胰岛素合成的能力。因此，我们假设人参提取物抑制胰腺β细胞线粒体中的UCP-2，促进胰岛素合成和抗凋亡（程序性细胞死亡机制）。为了检验这一假设，将去除血清的静止β细胞与或不与白细胞介素-1 β（IL-1β）（200 pg ml-1，一种诱导β细胞凋亡的细胞因子）和西洋参水提取物（25 μg/5 μl，给予0.5 ml培养物的威尔斯孔）一起培养24 h。我们评估了人参对UCP-2表达、胰岛素产生、抗/促凋亡因子Bcl-2/caspase-9表达和细胞ATP水平的影响。我们发现人参抑制UCP-2，下调caspase-9，同时增加ATP和胰岛素的产生/分泌，上调Bcl-2，减少细胞凋亡。这些结果表明，西洋参提取物通过抑制线粒体UCP-2，导致ATP水平和抗凋亡因子Bcl-2升高，同时下调促凋亡因子caspase-9，降低凋亡的发生，从而刺激胰岛素产生和防止β细胞丢失，这支持了这一假设。
American ginseng root displays the ability to achieve glucose homeostasis both experimentally and clinically but the unknown mechanism used by ginseng to achieve its therapeutic effects on diabetes limits its application. Disruption in the insulin secretion of pancreatic β cells is considered the major cause of diabetes. A mitochondrial protein, uncoupling protein-2 (UCP-2) has been found to play a critical role in insulin synthesis and β cell survival. Our preliminary studies found that the extracts of American ginseng inhibit UCP-2 expression which may contribute to the ability of ginseng protecting β cell death and improving insulin synthesis. Therefore, we hypothesized that ginseng extracts suppress UCP-2 in the mitochondria of pancreatic β cells, promoting insulin synthesis and anti-apoptosis (a programmed cell-death mechanism). To test the hypothesis, the serum-deprived quiescent β cells were cultured with or without interleukin-1β (IL-1β), (200 pg ml−1, a cytokine to induce β cell apoptosis) and water extracts of American ginseng (25 μg per 5 μl administered to wells of 0.5 ml culture) for 24 h. We evaluated effects of ginseng on UCP-2 expression, insulin production, anti-/pro-apoptotic factors Bcl-2/caspase-9 expression and cellular ATP levels. We found that ginseng suppresses UCP-2, down-regulates caspase-9 while increasing ATP and insulin production/secretion and up-regulates Bcl-2, reducing apoptosis. These findings suggest that stimulation of insulin production and prevention of β cell loss by American ginseng extracts can occur via the inhibition of mitochondrial UCP-2, resulting in increase in the ATP level and the anti-apoptotic factor Bcl-2, while down-regulation of pro-apoptotic factor caspase-9 occurs, lowering the occurrence of apoptosis, which support the hypothesis.
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