Effects of beta-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, we 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 micrograms/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 (Ra) and endogenous (EGP), hepatic (HGP), and renal (RGP) glucose production were measured by a combination of arteriovenous difference and peripheral infusion of [6-3H]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 Ra 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 micromol. 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 Ra 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 micromol. 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.
Cersosimo
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Department of Medicine, State University of New York at Stony Brook, Stony Brook, New York 11794-8154, USA.
Zaitseva
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Ajmal
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D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D003243:Consciousness; D004285:Dogs; D004837:Epinephrine / Q000097:blood; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000096:biosynthesis*; D006706:Homeostasis; D007003:Hypoglycemia / Q000139:chemically induced / Q000378:metabolism*; D007208:Indocyanine Green / Q000493:pharmacokinetics; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008102:Liver Circulation; D008297:Male; D009638:Norepinephrine / Q000097:blood; D011433:Propranolol / Q000494:pharmacology*; D012079:Renal Circulation
D000319:Adrenergic beta-Antagonists; D001786:Blood Glucose; D007328:Insulin; D005934:Glucagon; D011433:Propranolol; D007208:Indocyanine Green; D005947:Glucose; D009638:Norepinephrine; D004837:Epinephrine