Margolis R N, Curnow R T
Endocrinology. 1983 Dec;113(6):2113-9. doi: 10.1210/endo-113-6-2113.
The roles of insulin, adrenal corticol hormones, and nutritional factors in the regulation of hepatic glycogen metabolism were investigated by means of fasting and refeeding normal and adrenalectomized (ADX) rats. More specifically, the hypothesis in question in this study is that certain hepatic phosphoprotein phosphatases are targets of insulin action in liver. In anesthetized rats, the hepatic glycogen concentration and the activities of hepatic glycogen synthase, glycogen synthase phosphatase, glycogen phosphorylase, and phosphorylase phosphatase were correlated with peripheral plasma glucose and immunoreactive insulin levels. Hepatic phosphatase activities were measured in (soluble) the high speed supernatant and smooth endoplasmic reticulum (SER). Fasting resulted in expected diminutions in circulating glucose and insulin levels and loss of hepatic glycogen. These changes were greater in ADX rats. The percentage of hepatic glycogen synthase in the active or I form increased with fasting in normal rats, but did not change in ADX rats. Hepatic synthase phosphatase activities were decreased in SER by fasting in both normal and ADX rats, but to a much greater extent in the latter; soluble synthase phosphatase was much less affected by fasting. The percentage of phosphorylase in the active or a form was significantly decreased in normal, but not ADX, rats. Phosphorylase phosphatase activities were not significantly changed by fasting in any of the subcellular fractions in normal liver, but were increased in the hepatic SER of ADX rats. Refeeding fasted rats for 2 and 6 h resulted in increased hepatic glycogen, activation of glycogen synthase, and increased circulating levels of both insulin and glucose. Refeeding also caused increases in SER-associated synthase phosphatase activity in ADX animals. SER phosphorylase phosphatase activities were significantly increased by refeeding in normal rats, but were decreased in ADX rats. Regression analysis of the data suggested statistically significant positive correlations between insulin levels and SER synthase phosphatase activity in ADX animals, on the one hand, and SER synthase phosphatase and the percentage of synthase in the I form, on the other. No statistically significant correlation between insulin levels and phosphorylase phosphatase activities could be demonstrated. These results are compatible with the hypothesis that glycogen synthase phosphatase activity in liver, especially that associated with SER, is subject to physiological regulation by circulating levels of insulin. In contrast, phosphorylase phosphatase activity seems to be much less influenced by changes in the circulating insulin level. The results are compatible with the proposition that SER-associated phosphoprotein phosphatases are physiologically relevant in the regulation of hepatic glycogen metabolism.(ABSTRACT TRUNCATED AT 400 WORDS)
通过对正常大鼠和肾上腺切除（ADX）大鼠进行禁食和再喂食，研究了胰岛素、肾上腺皮质激素和营养因素在肝脏糖原代谢调节中的作用。更具体地说，本研究中所探讨的假设是，某些肝脏磷蛋白磷酸酶是肝脏中胰岛素作用的靶点。在麻醉的大鼠中，肝脏糖原浓度以及肝脏糖原合酶、糖原合酶磷酸酶、糖原磷酸化酶和磷酸化酶磷酸酶的活性与外周血浆葡萄糖和免疫反应性胰岛素水平相关。在（可溶性）高速上清液和平滑内质网（SER）中测量肝脏磷酸酶活性。禁食导致循环葡萄糖和胰岛素水平降低以及肝脏糖原减少。这些变化在ADX大鼠中更为明显。正常大鼠中，随着禁食，处于活性或I型的肝脏糖原合酶百分比增加，但在ADX大鼠中没有变化。正常大鼠和ADX大鼠禁食后，SER中的肝脏合酶磷酸酶活性均降低，但在后者中降低程度更大；可溶性合酶磷酸酶受禁食的影响小得多。正常大鼠而非ADX大鼠中，处于活性或a型的磷酸化酶百分比显著降低。正常肝脏中，任何亚细胞组分中的磷酸化酶磷酸酶活性在禁食后均无显著变化，但在ADX大鼠的肝脏SER中升高。对禁食大鼠再喂食2小时和6小时后，肝脏糖原增加、糖原合酶激活，胰岛素和葡萄糖的循环水平升高。再喂食还导致ADX动物中与SER相关的合酶磷酸酶活性增加。正常大鼠再喂食后，SER磷酸化酶磷酸酶活性显著增加，但在ADX大鼠中降低。对数据的回归分析表明，一方面，ADX动物中胰岛素水平与SER合酶磷酸酶活性之间存在统计学上显著的正相关，另一方面，SER合酶磷酸酶与I型合酶百分比之间也存在显著正相关。未证明胰岛素水平与磷酸化酶磷酸酶活性之间存在统计学上显著的相关性。这些结果与以下假设相符：肝脏中的糖原合酶磷酸酶活性，尤其是与SER相关的活性，受循环胰岛素水平的生理调节。相比之下，磷酸化酶磷酸酶活性似乎受循环胰岛素水平变化的影响小得多。这些结果与以下观点相符：与SER相关的磷蛋白磷酸酶在肝脏糖原代谢调节中具有生理相关性。（摘要截短至400字）
