2,5-Anhydro-D-mannitol increases hepatocyte sodium: transduction of a hepatic hunger stimulus?
2,5-Anhydro-D-mannitol increases hepatocyte sodium: transduction of a hepatic hunger stimulus?
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2,5-脱水-D-甘露醇增加肝细胞钠：肝脏饥饿刺激的转导？
DOI：
10.1016/s0167-4889(03)00098-3
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Osbakken,MaryD
中科院分区：
文献类型：
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作者：
Friedman,MarkI;Graczyk-Millbrandt,Grazyna;Ji,Hong;Rawson,NancyE;Osbakken,MaryD
为了检验肝细胞 ATP 减少通过钠泵活性变化转变成肝神经元信号的假设，我们使用 23 Na 核磁共振 (NMR) 波谱检查了刺激大鼠摄食行为的 2,5-脱水-d-甘露醇 (2,5-AM) 对细胞内钠水平的影响。在顺磁位移试剂铥(III)(1,4,7,10-四氮杂环十二烷-1,4,7,10-四(亚甲基膦酸酯))存在下，用2.5 mM 2,5-AM或果糖对悬浮在琼脂糖珠中的分离的肝细胞进行灌注。与单独灌注果糖或转移试剂相比，灌注 2,5-AM 在暴露后 15 分钟内开始降低肝细胞 ATP 并增加细胞内钠水平，在 30 分钟内达到基线的 120% 的最高水平，并在接下来的 90 分钟内逐渐下降。灌输果糖也会降低肝细胞 ATP，但降幅不到 2,5-AM 的一半，但对细胞钠水平没有显着影响。结果支持这样的假设：钠泵活性的变化可能参与将与肝细胞能量状态相关的饥饿刺激转化为饥饿信号。
To test the hypothesis that decreased hepatocyte ATP is transduced into a hepatic neuronal signal via a change in sodium pump activity, we examined the effect of 2,5-anhydro-d-mannitol (2,5-AM), which stimulates feeding behavior in rats, on intracellular sodium levels using23Na nuclear magnetic resonance (NMR) spectroscopy. Isolated hepatocytes suspended in agarose beads were superfused with either 2.5 mM 2,5-AM or fructose in the presence of the paramagnetic shift reagent, thulium(III)(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetra(methylenephosphonate)). Superfusion with 2,5-AM decreased hepatocyte ATP and increased intracellular sodium levels compared with superfusion with either fructose or shift reagent alone starting within 15 min of exposure, reaching a maximum level of 120% of baseline by 30 min and declining gradually thereafter over the next 90 min. Superfusion with fructose, which also decreased hepatocyte ATP but by less than half the amount seen with 2,5-AM, had no significant effect on cellular sodium levels. The results support the hypothesis that changes in sodium pump activity could participate in transducing a hunger stimulus associated with hepatocyte energy status into a signal for hunger.