Adrenergic, insulin, and work interactions with adenosine's effects on in situ myocardial glucose uptake

We have demonstrated that adenosine enhances insulin-stimulated myocardial glucose uptake in situ. In the present study we determined the role of adrenergic influences and myocardial work on insulin-stimulated myocardial glucose uptake while varying intracoronary adenosine concentrations. Under pentobarbital anesthesia we instrumented mongrel dogs to obtain blood pressure, heart rate, and arterial and coronary sinus blood samples for measuring oxygen and glucose concentrations. An electromagnetic blood flow probe around the circumflex coronary artery allowed determinations of blood flow, and calculation of myocardial oxygen (MVO2) and glucose (MGU) uptakes. Somatostatin was infused i.v. (0.8 microgram/kg.min-1) along with 10 mU/kg.min-1 regular insulin, and variable quantities of glucose to maintain euglycemia. Adenosine was infused at logarithmic incremental rates (0, 0.01, 0.1, 1.0, and 10 mumoles.min-1) for 30 min each into the main left coronary arteries. Adrenergic blockade was achieved with i.v. propranolol (70 micrograms/kg bolus followed by 5 micrograms/kg.min-1 infusion), and phentolamine (95 micrograms/kg bolus followed by 9.5 micrograms/kg.min-1 infusion). Insulin infusion significantly increased MGU. Adenosine increased the maximal value for insulin-stimulated glucose uptake. Adrenergic blockade alone did not alter insulin-stimulated MGU, but reduced heart rate and MVO2. When evaluated relative to MVO2 1.0 mumoles/ml adenosine infusion increased MGU independent of work-related changes in the presence or absence of adrenergic blockade. With an adenosine infusion rate of 10 mumoles/ml myocardial glucose uptake returned to baseline. These data also support our earlier speculation that the MGU response to adenosine may be biphasic. These results suggest that antagonism of adrenergic effects by adenosine cannot account for adenosine's ability to enhance insulin's effects on glucose uptake in the heart, but that work-related influences should be accounted for in interpreting results of this kind.