ADENOSINE RECEPTORS MEDIATE SYNERGISTIC STIMULATION OF GLUCOSE-UPTAKEAND TRANSPORT BY INSULIN AND BY CONTRACTIONS IN RAT SKELETAL-MUSCLE

The role of adenosine receptors in the regulation of muscle glucose up take by insulin and contractions was studied in isolated rat hindquart ers that were perfused with a standard medium containing no insulin or a submaximal concentration of 100 mu U/ml. Adenosine receptor antagon ism was induced by caffeine or 8-cyclopentyl-1,3-dipropylsantine (CPDP X). Glucose uptake and transport were measured before and during 30 mi n of electrically induced muscle contractions. Caffeine nor CPDPX affe cted glucose uptake in resting hindquarters. In contrast, the contract ion-induced increase in muscle glucose uptake was inhibited by 30-50% by caffeine, as well as by CPDPX, resulting in a 20-25% decrease in th e absolute rate of glucose uptake during contractions, compared with c ontrol values. This inhibition was independent of the rate of perfusat e flow and only occurred in hindquarters perfused with insulin added t o the medium. Thus, adenosine receptor antagonism inhibited glucose up take during simultaneous exposure to insulin and contractions only. Ac cordingly, caffeine inhibited 3-O-methylglucose uptake during contract ions only in oxidative muscle fibers that are characterized by a high sensitivity to insulin. In conclusion, the present data demonstrate A1 receptors to regulate insulin-mediated glucose transport in contracti ng skeletal muscle. The findings provide evidence that stimulation of sarcolemmic adenosine receptors during contractions is involved in the synergistic stimulation of muscle glucose transport by insulin and by contractions.