Schwartz A L, Raiha N C, Rall T W
Diabetes. 1975 Dec;24(12):1101-12. doi: 10.2337/diab.24.12.1101.
Glycogen accumulates in human fetal liver beginning at the eighth week of gestation. A parallel increase in total glycogen synthase activity is found, although the I-form activity remains low and constant throughout the first two thirds of gestation. Total phosphorylase activity increases slightly during this period, with the proportion in the active form amounting to about one half of the total throughout. After an initial rapid decline, the glycogen concentration in explants of human fetal liver remained constant for twenty to forty hours at about 20 per cent of the in vivo level. Incubation with glucagon, cyclic AMP (adenosine 3',5'-monophosphate) or its dibutyryl derivative markedly reduced tissue glycogen concentrations while insulin brought about a small increase. The effect of maximal doses of dibutyryl cyclic AMP and glucagon were the same, and the combination of agents produced no further effect. The response to dibutyryl cyclic AMP was apparent by one hour and maximal by three to six hours, whereas the response to insulin required about six hours to be detected, and it continued for at least eighteen hours. Insulin antagonized the glycogenolytic effect of low doses of glucagon or theophylline but was without significant effect in the presence of high glucagon concentrations. Glucagon stimulated cyclic AMP output from explants, and this effect was further augmented by theophylline. Insultin had no consistent effect on cyclic AMP output in either the presence or the absence of glucagon or theophylline. Incubation with dibutyryl cyclic AMP resulted in a decrease of glycogen synthase I-form activity, while insulin tended to increase this enzyme activity. In neither circumstance was the proportion of active phosphorylase altered. These results suggest that the regulation of glycogen levels in human fetal liver by cyclic AMP, glucagon, and insulin may entail alterations in the activity of glycogen synthase activity without necessitating alterations in phosphorylase activity. Cyclic AMP or glucagon was capable of depleting tissue glycogen stores in tissue from fetuses of six weeks' gestation. Insulin increased tissue glycogen concentrations in tissue from fetuses of seven or more weeks.
糖原在妊娠第8周开始在人胎儿肝脏中积累。总糖原合酶活性也相应增加，尽管在妊娠的前三分之二期间，I型活性一直较低且保持恒定。在此期间，总磷酸化酶活性略有增加，活性形式的比例在整个过程中约占总量的一半。人胎儿肝脏外植体中的糖原浓度在最初快速下降后，在约20%的体内水平上保持20至40小时恒定。用胰高血糖素、环磷酸腺苷（3',5'-单磷酸腺苷）或其二丁酰衍生物孵育可显著降低组织糖原浓度，而胰岛素则使其略有增加。最大剂量的二丁酰环磷酸腺苷和胰高血糖素的作用相同，联合使用这些药物没有进一步的效果。对二丁酰环磷酸腺苷的反应在1小时时明显，3至6小时时达到最大，而对胰岛素的反应需要约6小时才能检测到，并且至少持续18小时。胰岛素可拮抗低剂量胰高血糖素或茶碱的糖原分解作用，但在高浓度胰高血糖素存在时无显著作用。胰高血糖素刺激外植体产生环磷酸腺苷，茶碱可进一步增强这种作用。胰岛素在有无胰高血糖素或茶碱的情况下对环磷酸腺苷的产生均无一致影响。用二丁酰环磷酸腺苷孵育会导致糖原合酶I型活性降低，而胰岛素则倾向于增加该酶的活性。在这两种情况下，活性磷酸化酶的比例均未改变。这些结果表明，环磷酸腺苷、胰高血糖素和胰岛素对人胎儿肝脏中糖原水平的调节可能涉及糖原合酶活性的改变，而无需磷酸化酶活性的改变。环磷酸腺苷或胰高血糖素能够消耗6周妊娠胎儿组织中的糖原储备。胰岛素可增加7周或更大孕周胎儿组织中的糖原浓度。
