R. A. J. Challiss

The Hormone-Modulatory Effects of Adenosine in Skeletal Muscle

The interactive effects of insulin and the local hormone adenosine have been investigated in vitro in a number of skeletal muscle preparations. Insulin affects carbohydrate metabolism in these preparations by stimulating the rate of glucose transport and increasing the rate of glyco-gen synthesis. The concentration of insulin necessary to stimulate the rates of both these processes half-maximally is 100 μU/ml. Removal of endogenously produced adenosine by addition of adenosine deaminase increased specifically the sensitivity of the rate of glucose transport to insulin, whilst exerting no effect on the rate of glycogen synthesis. This suggests that the molecular basis of such a modulatory effect is at the “post-receptor” level. This was observed in soleus muscle (90% type I fibres) and extensor digitorum longus (90% type II fibres), but not in hemi-diaphragm. The insulin-modulatory effect of endogenous adenosine could be mimicked in a predictable manner by addition of adenosine-receptor agonists or antagonists. The possibility that adenosine was exerting this novel action on glucose metabolism in skeletal muscle by changes in intracellular cyclic AMP concentration has been studied. Our results suggest that this is unlikely; adenosine-receptor agonists have a weak stimulatory effect on adenylate cyclase and, in addition, elevation of intracellular cyclic AMP concentrations either by addition of dibutyryl cyclic AMP or β-adrenoceptor agonists do not directly affect the sensitivity of the rate of glucose transport to insulin.