The synergistic action of caffeine or adenosine on glucose stimulation of liver glycogen synthase phosphatase activity

Recent studies indicate that glucose directly stimulates synthase phosphatase activity in vitro but only at high, non-physiological concentrations. Present results demonstrate that at a physiological concentration glucose can be stimulatory, provided that an appropriate second effector is present. Caffeine and adenosine are examples of such effectors which act synergistically with glucose to enhance synthase phosphatase activity. Caffeine but not adenosine enhances glucose stimulation of phosphorylase phosphatase activity. In the absence of glucose, caffeine but not adenosine stimulates both synthase and phosphorylase phosphatase reactions. Thus, glucose regulation of glycogen synthase activation in vivo could require a second effector. Neither the identity nor source of such an effector is known. The putative regulator could be a mediator for a hormone such as insulin. The present work suggests that the chemical nature of the effector might be that of a derivatized purine of which nucleosides are an example.