The effects of lithium ions on glucose metabolism and the tissue content of monovalent cations were studied in rat hemidiaphragms incubated in vitro. The entrance of lithium ions into the cell was associated with an increase in the rate of glucose utilization and glycogen synthesis. As lithium was taken up by the tissue, there was a concomitant loss of potassium. The loss of potassium could not account for the stimulation of glucose metabolism produced by lithium and it was concluded that lithium ions per se increased glucose uptake and particularly glycogen synthesis. Preincubation of hemidiaphragms in media containing different concentrations of lithium ions resulted in an increase in the rate of glycogen synthesis during a subsequent incubation in the absence of lithium. The stimulation of glycogen formation was directly related to the tissue content of lithium. Lithium ions did not significantly alter the cyclic AMP content of the tissues under conditions at which the rate of glucose metabolism was markedly enhanced.
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