Facilitation by Adenosine of the Action of Insulin on the Accumulation of Adenosine 3′:5′‐Monophosphate, Lipolysis, and Glucose Oxidation in Isolated Fat Cells

The modulation of insulin action by adenosine has been studied in lipid and glucose metabolism of isolated rat fat cells. When 20000 cells per ml were incubated, insulin failed to antagonize the effect of 1 μM noradrenaline on adenosine 3′:5′‐monophosphate (cyclic AMP) levels and lipolysis. At high concentrations (100000 cells per ml) both parameters were strongly depressed by insulin. The addition of 0.1 μM adenosine to dilute cell suspensions decreased cyclic AMP accumulation in response to noradrenaline, but only marginally reduced lipolysis, thus producing the same situation as seen in concentrated cell suspensions. Furthermore, insulin antagonized the cyclic AMP accumulation and lipolysis caused by adenosine deaminase (1 μg per ml) or theophylline (0.3 mM). These two agents only moderately elevated cyclic AMP levels similar to the effect of noradrenaline in the presence of adenosine. These data strongly indicate that insulin is able to counteract hormone effects on cyclic AMP formation and lipolysis only at low cellular levels of the cyclic nucleotide. Stimulation of glucose oxidation by insulin in the range between 10 and 100 μU per ml was markedly enhanced in the presence of 0.1 μM adenosine when only 5000 fat cells per ml were incubated. On the other hand, adenosine deaminase reduced the action of insulin in the range between 1 and 300 μU per ml in concentrated cell suspensions (100000 cells per ml). The uptake of adenosine and the ATP levels in fat cells were not altered by insulin, except at high concentrations of adenosine (0.1 mM). Theophylline (0.5 mM) and dipyridamole (20μM) abolished the stimulatory effect of both insulin and adenosine on glucose oxidation. Increasing concentrations of adenosine were able to overcome the inhibitory effect of theophylline but not that of dipyridamole. These data suggest that adenosine may have an essential regulatory role which can be described as facilitation of insulin actions, even though different mechanisms apply to lipolysis and glucose oxidation.