Changes in internal pH caused by movement of fatty acids into and out of clonal pancreatic beta-cells (HIT).
Changes in internal pH caused by movement of fatty acids into and out of clonal pancreatic beta-cells (HIT).
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发表时间：
1994-08
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通讯作者：
J. Hamilton;V. Civelek;F. Kamp;K. Tornheim;B. Corkey
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作者：
J. Hamilton;V. Civelek;F. Kamp;K. Tornheim;B. Corkey
细胞需要不断流入的游离脂肪酸用于脂质再合成和代谢能量。脂肪酸也作为第二信使和调节通道活动。在胰腺β细胞中，脂肪酸对胰岛素分泌有急性和慢性影响。我们发现，在体外向胰腺β细胞中加入脂肪酸会导致细胞内pH值持续下降，这在加入脂肪酸后立即开始，并具有指数时间过程，t1/2约为60 s。加入白蛋白可在很大程度上逆转pH值下降。观察到的pH效应可以通过非离子化脂肪酸穿过质膜的被动扩散（“触发器”）来解释。脂肪酸二聚体的酸化和烷基胺的碱化也有利于转运的翻转机制，而不是蛋白质介导的机制。我们的方法首次提供了脂肪酸输入细胞的实时测量。显著的pH变化可能在介导脂肪酸的一些调节作用中是重要的，例如抑制糖酵解。
Cells require a constant influx of free fatty acids for lipid resynthesis and metabolic energy. Fatty acids also act as second messengers and modulate channel activities. In the pancreatic beta-cell, fatty acids have both acute and chronic effects on insulin secretion. We show that the addition of fatty acid to pancreatic beta-cells in vitro produces a persistent decrease in intracellular pH, which begins immediately after the addition of fatty acid and has an exponential time course with t1/2 approximately 60 s. The pH drop can be largely reversed by the addition of albumin. The observed pH effect can be explained by passive diffusion ("flip-flop") of un-ionized fatty acid across the plasma membrane. Acidification by a fatty acid dimer and alkalinization by an alkylamine also favor the flip-flop mechanism of transport rather than a protein-mediated mechanism. Our method provides for the first time a real-time measurement of fatty acid import into cells. The significant pH change may be important in mediating some of the regulatory effects of fatty acid, such as inhibition of glycolysis.