Knockdown of pyruvate carboxylase or fatty acid synthase lowers numerous lipids and glucose-stimulated insulin release in insulinoma cells.
Knockdown of pyruvate carboxylase or fatty acid synthase lowers numerous lipids and glucose-stimulated insulin release in insulinoma cells.
复制标题
丙酮酸羧化酶或脂肪酸合酶的敲低会降低胰岛素瘤细胞中大量脂质和葡萄糖刺激的胰岛素释放。
DOI：
10.1016/j.abb.2013.01.002
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发表时间：
2013
影响因子：
3.9
通讯作者：
Sampath,Harini
中科院分区：
文献类型：
--
作者：
MacDonald,MichaelJ;Hasan,NoamanM;Dobrzyn,Agnieszka;Stoker,ScottW;Ntambi,JamesM;Liu,Xueqing;Sampath,Harini
我们以前的研究表明，在INS-1 832/13胰岛素瘤细胞系中，回补酶丙酮酸羧化酶的敲低抑制了葡萄糖刺激的胰岛素释放和葡萄糖碳掺入脂质。我们现在表明，敲低脂肪酸合成酶（FAS）的mRNA和蛋白质也抑制葡萄糖刺激的胰岛素释放在这个细胞系。在葡萄糖刺激的丙酮酸羧化酶敲除细胞中，在与胰岛素分泌同时发生的时间过程中，许多磷脂、胆固醇酯、二酰甘油、甘油三酯和具有C14-C24侧链的单个脂肪酸的水平急剧降低约20%。在FAS敲除细胞中，葡萄糖碳掺入脂质以及磷脂和胆固醇酯种类的亚类的水平降低20-30%，而不抑制葡萄糖氧化。这些研究表明，快速脂质修饰对于正常葡萄糖刺激的胰岛素分泌是必不可少的。
We previously showed that knockdown of the anaplerotic enzyme pyruvate carboxylase in the INS-1 832/13 insulinoma cell line inhibited glucose-stimulated insulin release and glucose carbon incorporation into lipids. We now show that knockdown of fatty acid synthase (FAS) mRNA and protein also inhibits glucose-stimulated insulin release in this cell line. Levels of numerous phospholipids, cholesterol esters, diacylglycerol, triglycerides and individual fatty acids with C14–C24side chains were acutely lowered about 20% in glucose-stimulated pyruvate carboxylase knockdown cells over a time course that coincides with insulin secretion. In FAS knockdown cells glucose carbon incorporation into lipids and the levels of the subclasses of phospholipids and cholesterol ester species were lower by 20–30% without inhibition of glucose oxidation. These studies suggest that rapid lipid modification is essential for normal glucose-stimulated insulin secretion.