Miller T B, Vicalvi J J, Garnache A K
Am J Physiol. 1981 May;240(5):E539-43. doi: 10.1152/ajpendo.1981.240.5.E539.
Perfused livers from normal and alloxan-diabetic rats were studied to determine whether the diabetes-related decrease in glycogen synthase phosphatase was due to an alteration of the synthase molecule, an increase in synthase phosphatase activity inhibition by phosphorylase a, or generation of inhibitor of the phosphatase. With purified rat liver synthase as substrate for the phosphatase, the diabetic tissue remained 90-95% deficient in the ability to catalyze synthase D to I conversion, showing that the defect cannot be solely due to an altered substrate. When synthase phosphatase assays were carried out in the presence of rat liver glycogen phosphorylase antiserum, phosphatase activity remained 70-75% deficient in diabetic tissue. Therefore, the defect cannot be attributed to increased inhibition of synthase phosphatase by increased amounts of phosphorylase a. When synthase phosphatase assays were run by mixing extracts from normal and diabetic livers, phosphatase activity was additive, indicating that a phosphatase inhibitor was probably not involved in the phosphatase deficiency in the diabetic. These data are consistent with the hypothesis that the diabetes-related defect in glucose regulation of hepatic glycogen synthase is due to a molecular alteration or a deficiency of a specific glycogen synthase phosphatase.
对正常大鼠和四氧嘧啶糖尿病大鼠的灌注肝脏进行了研究，以确定糖尿病相关的糖原合酶磷酸酶减少是否是由于合酶分子的改变、磷酸化酶a对合酶磷酸酶活性抑制的增加，或磷酸酶抑制剂的产生。以纯化的大鼠肝脏合酶作为磷酸酶的底物时，糖尿病组织催化合酶D向I转化的能力仍有90 - 95%的缺陷，表明该缺陷不能仅仅归因于底物的改变。当在大鼠肝脏糖原磷酸化酶抗血清存在的情况下进行合酶磷酸酶测定时，糖尿病组织中的磷酸酶活性仍有70 - 75%的缺陷。因此，该缺陷不能归因于磷酸化酶a量的增加对合酶磷酸酶抑制作用的增强。当通过混合正常肝脏和糖尿病肝脏的提取物进行合酶磷酸酶测定时，磷酸酶活性是相加的，表明磷酸酶抑制剂可能与糖尿病中磷酸酶缺乏无关。这些数据与以下假设一致，即肝脏糖原合酶葡萄糖调节中与糖尿病相关的缺陷是由于分子改变或特定糖原合酶磷酸酶的缺乏。
