An effect of dexamethasone on glycogen metabolism in hepatocyte cultures
An effect of dexamethasone on glycogen metabolism in hepatocyte cultures
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DOI：
10.1016/0014-5793(80)81022-2
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发表时间：
1980-09
期刊：
影响因子：
3.5
通讯作者：
J. C. Redshaw
中科院分区：
文献类型：
--
作者：
J. C. Redshaw
类葡萄糖酸在通过代谢过程如糖原分解和糖原生成调节肝葡萄糖产生中的作用被称为“允许的”，因为它们对于维持细胞对通过环AMP起作用的激素的正常反应是必不可少的[11]。在肾上腺切除大鼠的离体灌注肝脏中，最大浓度的胰高血糖素正常激活磷酸化酶，但生理浓度则不能[2，3]。此外，缺乏肾上腺皮质类固醇导致总磷酸化酶活性显著降低，而活性磷酸化酶水平无变化[4]。据报道，体外灌注的肝脏中胰高血糖素刺激的环AMP蓄积正常或增加[2]。几个实验室报告称，肝脏中环腺苷酸依赖性蛋白激酶活性无变化。从正常或切除肾上腺的大鼠中获得的肝匀浆[5，6]，但其他人发现，在从切除肾上腺的大鼠中获得的肝匀浆中，I型环ASP依赖性蛋白激酶的活性只有正常活性的75%[7]。因此，尽管进行了广泛的研究，糖皮质激素参与肝糖原代谢调节的机制尚未明确。这部分是由于使用肾上腺切除的动物进行此类研究，以及伴随的这种体内系统固有的激素相互作用问题。原代单层培养的回肠细胞在完全确定的环境[S-IO]中存活数天，因此应提供一个有用的系统，用于研究糖皮质激素对糖原代谢的影响。因此，对肝甘氨酰-β-D-半乳糖苷酶的研究，
The role of glucoco~ icoids in the regulation of hepatic glucose production by metabolic processes such as glycogenolysis and gluconeogenesis has been termed ‘permissive’since they are essential for the maintenance of normal responsiveness of cells to hormones which act through cyclic AMP [11. In isolated perfused livers from adrenalectomised rats maximal concentrations of glucagon activate phosphorylase normally but physiological concentrations do not [2, 3]. Further, a lack of adrenal corticosteroids caused a significant reduction in total phosphorylase activity with no change in the level of active phosphorylase [4]. Glucagon-stimulated cyclic AMP accumulation by livers perfused in vitro has been reported as normal or increased [2]. Several laboratories have reported no change in cyclic AMP-dependent protein kinase activity in liver homage. nates obtained from normal or adrenalectomised rats [5, 6], but others have found only 75% of the normal activity of type I cyclic ASP-dependent protein kinase in liver homogenates obtained from adrenalectomised rats [7].Thus, despite extensive investigation, the mechanisms by which glucocorticoids participate in the regulation of hepatic glycogen metabolism have yet to be clearly defined. This is due in part to the use of adrenale~ tomised animals for such studies and the attendant problem of hormone interaction inherent in such an in vivo system. Ilepatocytes in primary monolayer culture are viable for several days in a totally defined en~ ronment[S-IO] and as such should provide a useful system in which to study glucocorticoid effects on glycogen metabolism. Therefore, a study of the enzymes of hepatic gly-