Actions of lithium ions and insulin on glucose utilization, glycogen synthesis and glycogen synthase in the isolated rat diaphragm

Abstract

The effects of lithium ions and insulin on carbohydrate metabolism of the isolated rat diaphragm were studied and compared. Like insulin, lithium ions caused a conversion of glycogen synthase D to the more active I form of the enzyme. Maximal activation of the enzyme was produced by about 5 mM LiCl. Lithium ions markedly increased glucose utilization and glycogen synthesis by the diaphragm, but the action of this ion appears to be exerted by a mechanism different from that of insulin, since the effects of maximal concentrations of the two agents are additive. In their action on glucose metabolism, lithium ions had a unique ability to direct the glucose taken up by the cell toward glycogen. Insulin and lithium ions had opposite effects on the tissue content of glucose 6-phosphate; insulin increased the tissue level of this metabolite, whereas lithium ions decreased it. ATP and creatine phosphate concentrations were not affected by insulin or lithium ions. The effects of lithium ions on carbohydrate metabolism are exerted at relatively low concentrations of Li, and our results indicate that significant alterations of carbohydrate metabolism may occur when therapeutic or toxic amounts of lithium salts are ingested by man.