Effects of β-adrenergic blockade on hepatic and renal glucose production during hypoglycemia in conscious dogs

To investigate the role of beta-adrenergic mechanisms in the counterregulatory response of the liver and kidney to hypoglycemia, me studied 10 dogs before and after a 2-h constant infusion of insulin (4 mU.kg(-1).min(-1)) either without (n = 4) or with (8 mu g/min, n = 6) propranolol and variable dextrose to maintain hypoglycemia, 7 days after surgical placement of sampling catheters in left renal and hepatic veins and femoral artery. Systemic glucose appearance (R-a) and endogenous (EGP), hepatic (HGP), and renal (RGP) glucose production were measured by a combination of arteriovenous difference and peripheral infusion of [6-H-3]glucose, renal blood flow with a flow probe, and hepatic plasma flow by indocyanine green clearance. Without beta-adrenergic blockade, arterial glucose decreased from 5.12 +/- 0.02 to 2.53 +/- 0.07 mmol/l, glucose R-a increased from 17.8 +/- 0.7 to 30.5 +/- 2.5 (P < 0.01) when EGP was 22.2 +/- 0.5, HGP from 13.5 +/- 1.1 to 19.3 +/- 1.3, and RGP from 2.4 +/- 1.0 to 8.6 +/- 0.9 mu mol.kg(-1).min(-1) (all P < 0.05). When propranolol was infused, glucose decreased from 5.97 +/- 0.02 to 2.71 +/- 0.03 mmol/l, glucose R-a increased from 16.3 +/- 1.0 to 25.1 +/- 1.6 when EGP was 9.9 +/- 0.4, HGP decreased from 14.4 +/- 0.7 to 10.4 +/- 0.6, and RGP decreased from 3.8 +/- 1.3 to 1.1 +/- 0.8 mu mol.kg(-1).min(-1) (all P < 0.05). Our data indicate that beta-adrenergic blockade impairs glucose recovery during sustained hypoglycemia, in part, by preventing the simultaneous compensatory increase in HGP and RGP.