DIFFERENTIAL-EFFECTS OF ALPHA AND BETA-ADRENERGIC-BLOCKADE ON GLUCOSE AND LACTATE METABOLISM DURING ACUTE STRESS

In this study we examined the role of α and β blockade on glucose and lactate metabolism during the acute stress of insulin-induced hypoglycemia. Three groups of conscious dogs with chronically fitted catheters in the femoral artery and in the femoral, portal, and hepatic veins were studied after an 18-hr fast. After a 1-hr basal period, hypoglycemia was induced with insulin infusion at 5 mU/kg-min for 3 hr. Group 1 received no other treatment. Groups 2 and 3 received, respectively, phentolamine (8 μg/kg-min) and propranolol (4 μg/kg- min) beginning 30 minutes before and throughout the experimental period. Despite similar hyperinsulinemia, plasma glucose dropped in Group 1 (from 115 ± 10 to 40 ± 3 mg/dl) and in Group 2 (from 110 ± 4 to 60 ± 3 mg/dl) but in Group 3 it was maintained at 45 ± 4 mg/dl by exogenous glucose infusion at a rate of 2.2 ± 0.4 mg/kg-min. Hepatic glucose production increased 50 ± 13%, 127 ± 30%, and 55 ± 30% in Groups 1, 2, and 3, respectively, within 60 minutes and was 56 ± 19%, 55 ± 17%, and -0.04 ± 12% during the last hour of the experiment. Glucose utilization did not change in Groups 1 and 2 but it increased in Group 3. Plasma lactate increased in Group 1 (from 850 ± 190 to 1,980 ± 450 μmol/L) and in Group 2 (985 ± 180 to 4,785 ± 500 μmol/L), while in Group 3 there was an early rise (to 695 ± 120 μmol/L) within 30 minutes that gradually dropped to near basal. Hepatic lactate balance (μmol/kg min) switched from a slight net release of 3 ± 4.5 to an average uptake of 13 ± 4 in Group 1 and to 40 ± 9 in Group 2. In Group 3 hepatic lactate release increased within 60 minutes and persisted throughout the experiment; this was associated with increased uptake of lactate across the hindlimb. These results indicate that catecholamines have a role in glucose counterregulation during insulin-induced hypoglycemia and there is an interaction between α and β receptors on muscle glycogenolysis and lactate release. With α blockade, there was enhanced β stimulation of muscle glycogenolysis and lactate release and the liver increased its uptake of lactate. With β blockade there was net hepatic production of lactate with increased uptake across the hindlimb. © 1990 by The Williams & Wilkins Co.