REGULATION OF MITOCHONDRIAL PYRUVATE CARBOXYLATION IN ISOLATED HEPATOCYTES BY ACUTE INSULIN-TREATMENT
REGULATION OF MITOCHONDRIAL PYRUVATE CARBOXYLATION IN ISOLATED HEPATOCYTES BY ACUTE INSULIN-TREATMENT
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DOI：
10.1042/bj2140451
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发表时间：
1983-01-01
影响因子：
4.1
通讯作者：
TITHERADGE, MA
中科院分区：
文献类型：
--
作者：
CHISHOLM, AB;ALLAN, EH;TITHERADGE, MA
研究了[大鼠]肝细胞急性胰岛素治疗对分离线粒体和filipin可渗透细胞中丙酮酸羧化的影响。单独用胰岛素刺激细胞对丙酮酸羧化或糖异生的基础速率没有影响，尽管它确实抑制了对胰高血糖素和儿茶酚胺的反应。胰岛素治疗不能对抗由血管紧张素或血管加压素刺激细胞引起的丙酮酸羧化率升高。胰岛素和糖异生激素都没有改变离体线粒体中可提取丙酮酸羧化酶的活性，这表明激素在离体完整细胞器水平上的作用是通过改变线粒体内效应分子的浓度来介导的，尤其是ATP和[ATP]/[ADP]比率和底物利用率。丙酮酸羧基化的改变与葡萄糖合成在对效应分子的敏感性、可能的第二信使和反应开始时间方面有很好的相关性，这表明通过该酶的通量的改变与它作为C3前体糖异生控制的重要位点是相容的。
The effect of acute insulin treatment of [rat] hepatocytes on pyruvate carboxylation in both isolated mitochondria and cells rendered permeable by filipin was examined. Challenging the cells with insulin alone had no effect on either the basal rate of pyruvate carboxylation or gluconeogenesis, although it did suppress the responses to both glucagon and catecholamines. Insulin treatment was unable to antagonize the enhanced rate of pyruvate carboxylation caused by stimulation of the cells with either angiotensin or vasopressin. Neither insulin nor the gluconeogenic hormones altered the total extractable pyruvate carboxylase activity in the isolated mitochondria, suggesting that the effect of hormones at the level of the isolated intact organelle was mediated via alterations in the intramitochondrial concentrations of effector molecules, notably ATP and the [ATP]/[ADP] ratio and substrate availability. The alterations in pyruvate carboxylation correlate well with glucose synthesis in terms of sensitivity to effector molecules, putative 2nd messengers and time of onset of the response, indicating that alterations in the flux through this enzyme are compatible with it being an important site in the control of gluconeogenesis from C3 precursors.