REMOVAL OF ADENOSINE DECREASES THE RESPONSIVENESS OF MUSCLE GLUCOSE-TRANSPORT TO INSULIN AND CONTRACTIONS

Adenosine in the extracellular space modulates stimulated glucose tran sport in striated muscle. In the heart and in adipocytes, adenosine po tentiates insulin-stimulated glucose transport. There is controversy r egarding the effect of adenosine in skeletal muscle, with reports of b oth an inhibitory effect and no effect, on insulin-stimulated glucose transport. We found that, in rat epitrochlearis and soleus muscles, re moving adenosine with adenosine deaminase or blocking its action with the adenosine receptor blocker CPDPX markedly reduces the responsivene ss of glucose transport to stimulation by 1) insulin alone, 2) contrac tions alone, and 3) insulin and contractions in combination. Measureme nt of the increase in GLUT4 at the cell surface in response to a maxim ally effective insulin stimulus in the epitrochlearis muscle, using th e exofacial label ATB-[H-3]BMPA, showed that adenosine deaminase treat ment markedly reduces cell-surface GLUT4 labeling. The reduction in ce ll-surface GLUT4 labeling was similar in magnitude to the decrease in maximally insulin-stimulated glucose transport activity in adenosine d eaminase-treated muscles. These results show that adenosine potentiate s insulin- and contraction-stimulated glucose transport in skeletal mu scle by enhancing the increase in GLUT4 at the cell surface and raise the possibility that decreased adenosine production or action could pl ay a causative role in insulin resistance.