INHIBITION OF GLUCONEOGENESIS IN ISOLATED RAT HEPATOCYTES AFTER CHRONIC TREATMENT WITH PHENOBARBITAL
INHIBITION OF GLUCONEOGENESIS IN ISOLATED RAT HEPATOCYTES AFTER CHRONIC TREATMENT WITH PHENOBARBITAL
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DOI：
10.1042/bj2800663
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发表时间：
1991-12-15
影响因子：
4.1
通讯作者：
LEVERVE, XM
中科院分区：
文献类型：
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作者：
ARGAUD, D;HALIMI, S;LEVERVE, XM
在从禁食24 h的苯巴比妥预处理大鼠中分离的肝细胞中研究了葡萄糖异生。在封闭小瓶孵育中，由乳酸盐（20 mmol/l）和丙酮酸盐（2 mmol/l）、丙氨酸（20 mmol/l）或谷氨酰胺（20 mmol/l）产生的葡萄糖被抑制约30- 45%，但甘油代谢不受影响。在用乳酸和丙酮酸（比例10：1）灌注的肝细胞中，葡萄糖的产生被抑制了50%，即使在低的产酸通量下。从几个稳定状态下的产气通量的产气中间体的测定中，我们发现磷酸烯醇式丙酮酸和葡萄糖产生速率（J（葡萄糖））之间存在单一关系，而在对照组和苯巴比妥预处理的肝细胞中，胞质草酰乙酸和J（葡萄糖）之间存在两条不同的曲线。通过使用3-巯基吡啶甲酸酯来确定磷酸烯醇式丙酮酸羧激酶的流量控制系数，我们发现苯巴比妥预处理导致该系数从0.3（对照组）增加到0.8（苯巴比妥组）。这些观察结果得到证实的发现，磷酸烯醇式丙酮酸羧激酶的活性降低了50%苯巴比妥治疗后。因此，我们的结论是，苯巴比妥的抑制作用，对pneumeogenesis是由于，至少部分，通过磷酸烯醇式丙酮酸羧激酶的流量减少。
Gluconeogenesis was studied in hepatocytes isolated from phenobarbital-pretreated rats fasted for 24 h. In closed vial incubations, glucose production from lactate (20 mmol/l) and pyruvate (2 mmol/l), alanine (20 mmol/l) or glutamine (20 mmol/l) was suppressed by about 30-45%, although glycerol metabolism was not affected. In hepatocytes perifused with lactate and pyruvate (ratio 10:1), glucose production was inhibited by 50%, even at low gluconeogenic flux. From the determination of gluconeogenic intermediates at several steady states of gluconeogenic flux, we have found a single relationship between phosphoenolpyruvate and the rate of glucose production (J(glucose)), and two different curves between cytosolic oxaloacetate and J(glucose) in controls and in phenobarbital-pretreated hepatocytes. By using 3-mercaptopicolinate to determine the flux control coefficient of phosphoenolpyruvate carboxykinase we found that phenobarbital pretreatment led to an increase in this coefficient from 0.3 (controls) to 0.8 (phenobarbital group). These observations were confirmed by the finding that the activity of phosphoenolpyruvate carboxykinase was decreased by 50% after phenobarbital treatment. Hence we conclude that the inhibitory effect of phenobarbital on gluconeogenesis is due, at least partly, to a decrease in the flux through phosphoenolpyruvate carboxykinase.