Effects of dipyridamole on adenosine concentration, insulin sensitivity and glucose utilisation in soleus muscle of the rat.

Adenosine has been shown to modulate the sensitivity of skeletal muscle to insulin (Budohoski et al. 1984). In an attempt to further characterize the modulatory action of adenosine on insulin sensitivity in skeletal muscle we have investigated the effect of the nucleoside transport inhibitor dipyridamole in isolated incubated soleus muscle strips. At a concentration of 50 microM, dipyridamole increased the concentration of adenosine in the soleus muscle by 36% and in the incubation medium by 32%. At this concentration of dipyridamole, the basal rates (in the presence of 1 microunit of insulin/ml) of lactate formation, 2-deoxy [2,6-3H]glucose phosphorylation and glucose oxidation were decreased by 48%, 43% and 47% respectively, whilst the rate of glycogen synthesis was unaffected. Insulin-stimulated rates (in the presence of 10,000 microunits of insulin/ml) of lactate formation, 2-deoxy [2,6-3H] glucose phosphorylation, glycogen synthesis and glucose oxidation were decreased by 70%, 30%, 26% and 20% respectively in the presence of 50 microM dipyridamole. Although 50 microM dipyridamole was required to exert a significant effect on medium and soleus muscle adenosine concentrations, statistically significant effects on glycolytic rate were observed at concentrations as low as 2 microM dipyridamole. It is concluded that the results are not consistent with dipyridamole exerting an effect on skeletal muscle carbohydrate metabolism solely through elevation of the intracellular or interstitial adenosine concentration, but strongly suggest that dipyridamole inhibits glucose transport and/or phosphorylation in skeletal muscle.