Miller T B, Garnache A, Cruz J
J Biol Chem. 1984 Oct 25;259(20):12470-4.
Activation of glycogen synthase in the perfused rat liver is defective in severely diabetic rats. In the present study, activation of glycogen synthase by glucose and increased incorporation of [14C]glucose into glycogen by insulin are defective in hepatocytes isolated from alloxan diabetic rats. Acute activation of glycogen synthase in hepatocytes isolated from diabetic rats was restored by treatment of the rats with insulin in vivo. Restoration of synthase activation was not achieved by incubation of hepatocytes in the presence of insulin in vitro for up to 12 h. When isolated hepatocytes from diabetic rats were placed in primary culture in a serum-free defined medium over a 3-day period, glycogen synthesis was partially restored by cortisol and triiodothyronine and dramatically increased by insulin. Concomitant with restoration of [14C]glycogen synthesis was an insulin-mediated increase in glycogen synthase I and synthase phosphatase activity. Restoration of regulation of glycogen synthesis in primary cultures of hepatocytes from diabetic rats by insulin required the presence of cortisol and triiodothyronine. Primary cultures of hepatocytes from normal rats did not require triiodothyronine for insulin to effect glycogenesis over a 3-day period. These data demonstrate that insulin acts in a chronic manner in concert with other hormones to control synthase phosphatase activity, an effect which may be influencing acute control of hepatic glycogen synthesis.
在灌注的大鼠肝脏中，糖原合酶的激活在重度糖尿病大鼠中存在缺陷。在本研究中，从四氧嘧啶糖尿病大鼠分离的肝细胞中，葡萄糖对糖原合酶的激活以及胰岛素使[14C]葡萄糖掺入糖原的增加均存在缺陷。通过在体内用胰岛素治疗糖尿病大鼠，可恢复从糖尿病大鼠分离的肝细胞中糖原合酶的急性激活。在体外将肝细胞与胰岛素一起孵育长达12小时，未能实现合酶激活的恢复。当将糖尿病大鼠分离的肝细胞在无血清限定培养基中进行原代培养3天时，皮质醇和三碘甲状腺原氨酸可部分恢复糖原合成，而胰岛素则使其显著增加。与[14C]糖原合成的恢复相伴的是胰岛素介导的糖原合酶I和合酶磷酸酶活性的增加。胰岛素恢复糖尿病大鼠肝细胞原代培养中糖原合成的调节需要皮质醇和三碘甲状腺原氨酸的存在。在3天的时间里，正常大鼠肝细胞的原代培养不需要三碘甲状腺原氨酸，胰岛素就能发挥糖原生成作用。这些数据表明，胰岛素与其他激素协同以慢性方式发挥作用，以控制合酶磷酸酶活性，这一作用可能影响肝脏糖原合成的急性调控。
