Adenosine and Insulin Mediate Glucose Uptake in Normoxic Rat Hearts by Different Mechanisms

The effect of adenosine (ADO) and its interaction with insulin (I) on myocardial glucose uptake was evaluated in the normoxic isolated rat heart using 2-[3H]deoxyglucose. Isovolumic hearts were perfused at constant flow with a nonrecirculating bicarbonate buffer containing 5.5 mM glucose as the sole substrate. After a 30-min equilibration period, the glucose and extracellular ([14C]sucrose) tracers were infused for 15 min before initiation of the 15-min experimental period. Both 100 microM ADO and 4 mU/ml I significantly increased glucose uptake (GU) compared with control values (in mumol.min-1 x g-1: ADO = 0.34 +/- 0.03, I = 0.44 +/- 0.03, control = 0.23 +/- 0.02; P < 0.05). In combination, ADO and I produced an additive increase in GU (0.54 +/- 0.03; P < 0.05 vs. control). The mechanism of enhanced GU by ADO and I was investigated with the glucose uptake inhibitors phloridzin (PZ) and phloretin (PT), each of which has a unique site of action on the cell membrane. ADO-mediated GU was completely blocked by 3 mM PZ (ADO + PZ = 0.20 +/- 0.01; P = NS vs. control), but I-stimulated GU was unaffected (I + PZ = 0.38 +/- 0.03; P = NS vs. I). Only GU attributable to ADO was blocked by PZ infused with ADO and I (ADO + I + PZ = 0.43 +/- 0.03; P = NS vs. I). Both ADO- and I-mediated GU were inhibited by 100 microM PT.(ABSTRACT TRUNCATED AT 250 WORDS)