5-Iodotubercidin and proglycosyn: a comparison of two glycogenic compounds in hepatocytes from fasted rats.

ABSTRACT

5-Iodotubercidin (Itu) and proglycosyn (Pro) have similar glycogenic properties. To compare their mechanisms of action, we tested them in hepatocytes from fasted rats. We show that both compounds are similar in that they stimulated glycogen synthesis, increased the concentration of synthase a, decreased that of phosphorylase a and lowered the concentration of F-2,6-P2 in the presence of glucose, lactate-pyruvate and amino acids. However, when amino acids were absent, Pro was the better stimulator of glycogenesis than Itu and in combination they elevated glycogen and synthase a concentrations synergistically. Further they differ in that (1) Itu enhanced the levels of cyclic AMP whereas Pro did not; (2) Pro depressed glucose production from gluconeogenic substrates, whereas Itu stimulated this process; (3) the inhibition of F-2,6-P2 formation and glycolysis by Pro became much weaker than that by Itu when glucose concentrations were raised from 10 to 20 mM. Inhibition of glycolysis but not that of glycogen synthesis was partly due to a phosphorylated metabolite of Itu. The present study indicates that despite their similar glycogenic effects, Itu and Pro do not share a common mechanism of action. Further, the inhibition of glycolysis and F-2,6-P2 formation by Itu cannot be explained if it acts solely as a general inhibitor of protein kinases.