Stalmans W, Bollen M, Mvumbi L
Diabetes Metab Rev. 1987 Jan;3(1):127-61. doi: 10.1002/dmr.5610030107.
Investigations in our laboratory have shown that the activity of glycogen synthase phosphatase in the liver is shared by at least two functionally distinct proteins: a G-component, which is tightly associated with glycogen particles, and a soluble S-component. Most preparations of glycogen synthase-b that are isolated from the liver of fed glucagon-treated animals require the presence of both components in order to be converted to synthase-a. The G-component is subject to control mechanisms that do not affect the S-component. Its activity is strongly inhibited by phosphorylase-a. This feature explains why glycogen synthesis and glycogenolysis do not normally occur simultaneously, except in the glycogen-depleted liver, where a futile cycle may occur. Experiments in vitro have shown that a minimal glycogen concentration is required to ensure the interaction between the G-component and phosphorylase-a. The G-component is also selectively inhibited by Ca2+, and the magnitude of this inhibition depends markedly on the glycogen concentration. The latter inhibition is probably one of the mechanisms by which cyclic adenosine monophosphate (cAMP)-independent glycogenolytic agents achieve the inactivation of glycogen synthase in the liver. Glucocorticoid hormones and insulin are required for the induction and/or maintenance of the G-component in the liver. During the development of the fetal rat, glucocorticoids induce the G-component in the liver. This is an essential event in the glucocorticoid-triggered deposition of glycogen in the fetal liver. A functional adrenal cortex is also required in the adult animal to prevent a loss of the capacity for hepatic glycogen storage during starvation. The latter capacity depends on the concentration of functional G-component in the liver. Chronic diabetes causes a similar functional loss. However, the effect of glucocorticoids is not mediated by a putative secretion of insulin.
我们实验室的研究表明，肝脏中糖原合酶磷酸酶的活性至少由两种功能不同的蛋白质共同承担：一种是紧密结合糖原颗粒的G组分，另一种是可溶性的S组分。从喂食胰高血糖素处理动物肝脏中分离得到的大多数糖原合酶-b制剂，需要同时存在这两种组分才能转化为合酶-a。G组分受不影响S组分的调控机制的控制。其活性受到磷酸化酶-a的强烈抑制。这一特性解释了为什么糖原合成和糖原分解通常不会同时发生，除非在糖原耗尽的肝脏中可能会出现无效循环。体外实验表明，需要最低限度的糖原浓度来确保G组分与磷酸化酶-a之间的相互作用。G组分也受到Ca2+的选择性抑制，这种抑制的程度明显取决于糖原浓度。后一种抑制可能是环磷酸腺苷（cAMP）非依赖性糖原分解剂使肝脏中糖原合酶失活的机制之一。糖皮质激素和胰岛素是肝脏中G组分诱导和/或维持所必需的。在胎鼠发育过程中，糖皮质激素诱导肝脏中的G组分。这是糖皮质激素触发胎肝糖原沉积过程中的一个重要事件。成年动物也需要有功能的肾上腺皮质来防止饥饿期间肝糖原储存能力的丧失。后一种能力取决于肝脏中功能性G组分的浓度。慢性糖尿病会导致类似的功能丧失。然而，糖皮质激素的作用不是由假定的胰岛素分泌介导的。
