Stimulation of rat liver glycogen synthesis by the adenosine kinase inhibitor 5-iodotubercidin.

The adenosine kinase inhibitor 5-iodotubercidin (Itu) was found to have the following effects on glycogen metabolism in hepatocytes of fasted rats. (1) Itu strongly stimulated glycogen synthesis from different substrates (glucose, lactate plus pyruvate, dihydroxyacetone, glycerol and fructose). In cells incubated with these substrates, the well-known stimulating effect of amino acids and that of Itu was more than additive. (2) In parallel with the increase in glycogen deposition, there was an increase in synthase a and a decrease in phosphorylase a concentrations after administration of Itu. Synthase a was increased by Itu and amino acids in an additive manner, whereas the observed activation of phosphorylase after addition of amino acids was antagonized by Itu. (3) In contrast with amino acids, Itu increased neither the cell volume nor the aspartate and glutamate concentrations. (4) Itu enhanced the levels of cyclic AMP. The stimulation of glycogen deposition in the presence of Itu persisted when the cyclic AMP concentration was further increased by adenosine or 2-chloroadenosine. (5) Itu decreased the concentration of ATP, but its effects on glycogen synthesis, synthase a and phosphorylase a concentrations persisted when the ATP catabolism was prevented by adenosine. (6) The effect of Itu on glycogen synthesis was not the result of inhibition of adenosine kinase, since 5'-amino-5'-deoxyadenosine, another inhibitor of this enzyme, had no effect on glycogen deposition.