Rodriguez-Gil J E, Fernández-Novell J M, Barberá A, Guinovart J J
Unit of Reproduction, Autonomous University of Barcelona, Bellaterra, E-08193, Spain.
Arch Biochem Biophys. 2000 Mar 15;375(2):377-84. doi: 10.1006/abbi.1999.1679.
Oral administration of lithium carbonate to fed-healthy rats strongly decreased liver glycogen content, despite the simultaneous activation of glycogen synthase and the inactivation of glycogen phosphorylase. The effect seemed to be related to a decrease in glucose 6-phosphate concentration and to a decrease in glucokinase activity. Moreover, in these animals lithium markedly decreased liver fructose 2,6-bisphosphate, which could be a consequence of the fall in glucose 6-phosphate and of the inactivation of 6-phosphofructo-2-kinase. Liver pyruvate kinase activity and blood insulin also decreased after lithium administration. Lower doses of lithium carbonate had less intense effects. Lithium administration to starved-healthy and fed-streptozotocin-diabetic rats caused a slight increase in blood insulin, which was simultaneous with increases in liver glycogen, glucose 6-phosphate, and fructose 2, 6-phosphate. Glucokinase, 6-phosphofructo-2-kinase, and pyruvate kinase activities also increased after lithium administration in starved-healthy and fed-diabetic rats. Lithium treatment activated glycogen synthase and inactivated glycogen phosphorylase in a manner similar to that observed in fed-healthy rats. Glycemia was not modified in any group of animals. These results indicate that lithium acts on liver glycogen metabolism in vivo in at least two different ways: one related to changes in insulinemia, and the other related to the direct action of lithium on the activity of some key enzymes of liver glucose metabolism.
给健康的喂食大鼠口服碳酸锂，尽管同时激活了糖原合酶并使糖原磷酸化酶失活，但肝脏糖原含量仍大幅降低。这种作用似乎与6-磷酸葡萄糖浓度降低和葡萄糖激酶活性降低有关。此外，在这些动物中，锂显著降低了肝脏果糖2,6-二磷酸，这可能是6-磷酸葡萄糖下降和6-磷酸果糖-2-激酶失活的结果。给予锂后，肝脏丙酮酸激酶活性和血液胰岛素水平也降低。较低剂量的碳酸锂作用较弱。给饥饿的健康大鼠和喂食链脲佐菌素诱导的糖尿病大鼠服用锂后，血液胰岛素略有增加，同时肝脏糖原、6-磷酸葡萄糖和果糖2,6-二磷酸也增加。在饥饿的健康大鼠和喂食糖尿病大鼠中给予锂后，葡萄糖激酶、6-磷酸果糖-2-激酶和丙酮酸激酶活性也增加。锂治疗激活糖原合酶并使糖原磷酸化酶失活，其方式与在喂食的健康大鼠中观察到的相似。任何一组动物的血糖水平均未改变。这些结果表明，锂在体内对肝脏糖原代谢至少有两种不同的作用方式：一种与胰岛素血症的变化有关，另一种与锂对肝脏葡萄糖代谢某些关键酶活性的直接作用有关。
