Role of adenosine in regulating glucose uptake during contractions and hypoxia in rat skeletal muscle

1. The effect of A(1)-adenosine receptor antagonism via 8-cyclopentyl-1,3 - dipropyl-xanthine (CPDPX) on the stimulation of skeletal muscle glucose upt ake by contractions and hypoxia was investigated in isolated perfused rat h indquarters. The standard perfusate contained either no insulin or a submax imal insulin concentration at 100 mu U ml(-1). 2. Muscles were stimulated to contract for 45 min Ey intermittent tetanic s timulation of the sciatic nerve. Hypoxia was induced by reducing perfusate haematocrit from 30% to 10% on the one hand, and by switching the gassing o f the perfusate from a 35% to a 0% O-2 mixture for 60 min on the other hand . The effect of contractions and hypoxia alone, or in combination, was inve stigated. 3. Hypoxia-induced muscle glucose uptake was not altered by CPDPX in the ab sence or presence of insulin. In contrast, contraction-induced glucose upta ke was reduced by similar to 25% (P < 0.05) by exposure of muscles to CPDPX . CPDPX did not affect hindlimb glucose uptake either before or after contr actions. 4. The increment of muscle glucose uptake during hypoxia combined with cont ractions was greater (P < 0.05) than the effect of hypoxia alone. 5. The current findings provide evidence that the mechanism by which hypoxi a stimulates muscle glucose uptake is, at least in part, different from the mechanism of glucose uptake stimulation by contractions, because (i) A(1)- adenosine receptors regulate insulin-mediated glucose uptake in muscle duri ng contractions but not during hypoxia and (ii) submaximal hypoxia and cont ractions are additive stimuli to muscle glucose uptake.