AJP - Regulatory, Integrative and Comparative Physiology, Vol 264, Issue 5 984-R991, Copyright © 1993 by American Physiological Society
Beta-adrenergic blockade attenuates insulin resistance induced by tumor necrosis factor
C. H. Lang
Department of Surgery, State University of New York, Stony Brook 11794.
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.
