title: Adenosine and insulin mediate glucose uptake in normoxic rat hearts by different mechanisms.
abstract: 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)
authors.affiliation: Department of Physiology, University of Virginia Health Sciences Center, Charlottesville 22908.
authors.forename: D A
authors.initials: DA
authors.lastname: Angello
authors.forename: R M
authors.initials: RM
authors.lastname: Berne
authors.forename: N M
authors.initials: NM
authors.lastname: Coddington
mesh_terms: D000241:Adenosine / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D005947:Glucose / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption; D010693:Phloretin / Q000494:pharmacology; D010695:Phlorhizin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values
chemical_list: D007328:Insulin; D010695:Phlorhizin; D005947:Glucose; D000241:Adenosine; D010693:Phloretin