Beta-adrenergic blockade attenuates insulin resistance induced by tumor necrosis factor.
The macrophage secretory product tumor necrosis factor (TNF) impairs insulin action on peripheral glucose uptake and hepatic glucose output. Because circulating catecholamines are also elevated by TNF, the present study was performed to determine the role of the adrenergic system in eliciting the insulin resistance. Human recombinant TNF (1 microgram.h-1.kg-1) was infused intravenously into chronically catheterized fasted rats for approximately 18 h. Before TNF, an infusion of either saline, propranolol (nonselective beta-antagonist), atenolol (selective beta 1-antagonist), or phentolamine (alpha-antagonist) was started and continued throughout the experimental protocol. Infusion of either the alpha- or beta-receptor antagonist failed to prevent the TNF-induced increase in basal glucose uptake or hepatic glucose output. Under euglycemic hyperinsulinemic conditions, whole body glucose disposal was lower in TNF-infused rats than in control animals. This resulted from a decreased rate of insulin-stimulated glucose uptake by skeletal muscle, skin, and intestine. In propranolol-infused rats, but not in those receiving atenolol or phentolamine, the TNF-induced decrease in whole body glucose uptake was partially prevented. Propranolol attenuated the development of peripheral insulin resistance by selectively preventing the decrease in glucose uptake by skeletal muscle but not by skin and ileum. Propranolol was also able to ameliorate the hepatic insulin resistance produced by TNF. These results suggest that beta-adrenergic stimulation, probably mediated by a beta 2-adrenergic mechanism, is partially responsible for the development of both peripheral and hepatic insulin resistance in animals infused with TNF.
Lang
C H
CH
Department of Surgery, State University of New York, Stony Brook 11794.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D008297:Male; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D007328:Insulin; D014409:Tumor Necrosis Factor-alpha; D001262:Atenolol; D011433:Propranolol; D005947:Glucose; D010646:Phentolamine