Adrenergic blockade prevents endotoxin-induced increases in glucose metabolism.
Combined alpha- and beta-adrenergic blockade was used to investigate the role of catecholamines in endotoxin-induced elevations in glucose kinetics. Glucose kinetics were measured before and for 4 h after the injection of endotoxin [100 micrograms/100 g body wt iv, 30% lethal dose (LD30) at 24 h]. Adrenergic blockade was achieved by the bolus injection of phentolamine and propranolol followed by their continuous infusion. Endotoxin-treated rats exhibited a transient hyperglycemia and sustained (greater than 4 h) increase in plasma lactate concentration, as well as elevated rates of glucose appearance (Ra, 83%), disappearance (Rd, 58%), recycling (160%), and metabolic clearance (23%). Adrenergic blockade prevented endotoxin-induced increases in plasma glucose concentration, Ra, Rd, and recycling but not glucose clearance. The increase in plasma lactate concentration was blunted by 35%. After 2 h, endotoxic animals infused with adrenergic antagonists developed hypoglycemia, which may have resulted from an increased plasma insulin concentration. The attenuation of elevated glucose turnover by adrenergic blockade in the endotoxin-treated animals was not due to a reduction in plasma glucagon level or differences in plasma insulin concentration. Administration of the alpha- or beta-adrenergic antagonists separately blunted but did not prevent endotoxin-induced changes in glucose kinetics, and therefore the efficacy of the adrenergic blockade could not be assigned to a single receptor class. These results indicate that catecholamines are important contributory factors to many of the early alterations in carbohydrate metabolism observed during endotoxemia.
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D004731:Endotoxins / Q000037:antagonists & inhibitors*; D004926:Escherichia coli; D005934:Glucagon / Q000097:blood; D005947:Glucose / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects; D007773:Lactates / Q000097:blood; D008297:Male; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D001786:Blood Glucose; D004731:Endotoxins; D007773:Lactates; D005934:Glucagon; D011433:Propranolol; D005947:Glucose; D010646:Phentolamine