Lithium's effects on rat liver glucose metabolism in vivo

Oral administration of lithium carbonate to fed-healthy rats strongly decre ased liver glycogen content, despite the simultaneous activation of glycoge n synthase and the inactivation of glycogen phosphorylase. The effect seeme d to be related to a decrease in glucose g-phosphate concentration and to a decrease in glucokinase activity. Moreover, in these animals lithium marke dly decreased liver fructose 2,6-bisphosphate, which could be a consequence of the fall in glucose g-phosphate and of the inactivation of 6-phosphofru cto-2-kinase. Liver pyruvate kinase activity and blood insulin also decreas ed after lithium administration. Lower doses of lithium carbonate had less intense effects. Lithium administration to starved-healthy and fed-streptoz otocin-diabetic rats caused a slight increase in blood insulin, which was s imultaneous with increases in liver glycogen, glucose 6-phosphate, and fruc tose 2,6-phosphate. Glucokinase; 6-phosphofructo-2-kinase, and pyruvate kin ase activities also increased after lithium administration int starved-heal thy and fed-diabetic rats. Lithium treatment activated glycogen synthase an d inactivated glycogen phosphorylase in a manner similar to that observed i n fed-healthy rats. Glycemia was not modified in any group of animals. Thes e results indicate that lithium acts on liver glycogen metabolism in vivo i n at least two different ways: one related to changes in insulinemia, and t he other related to the direct action of lithium on the activity of some ke y enzymes of liver glucose metabolism. (C) 2000 Academic Press.