β-Adrenergic blockade attenuates insulin resistance induced by tumor necrosis factor

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Abstract

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 μg · h-1 · kg-1) was infused intravenously into chronically catheterized fasted rats for ~18 h. Before TNF, an infusion of either saline, propranolol (nonselective β-antagonist), atenolol (selective β1-antagonist), or phentolamine (α-antagonist) was started and continued throughout the experimental protocol. Infusion of either the α- or β-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 β-adrenergic stimulation, probably mediated by a β2-adrenergic mechanism, is partially responsible for the development of both peripheral and hepatic insulin resistance in animals infused with TNF.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume264
Issue number5 33-5
StatePublished - 1993

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Adrenergic Agents
Insulin Resistance
Tumor Necrosis Factor-alpha
Glucose
Propranolol
Atenolol
Phentolamine
Liver
Skeletal Muscle
Insulin
Skin
Ileum
Vascular Resistance
Catecholamines
Intestines
Macrophages

All Science Journal Classification (ASJC) codes

  • Physiology

Cite this

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title = "β-Adrenergic blockade attenuates insulin resistance induced by tumor necrosis factor",
abstract = "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 μg · h-1 · kg-1) was infused intravenously into chronically catheterized fasted rats for ~18 h. Before TNF, an infusion of either saline, propranolol (nonselective β-antagonist), atenolol (selective β1-antagonist), or phentolamine (α-antagonist) was started and continued throughout the experimental protocol. Infusion of either the α- or β-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 β-adrenergic stimulation, probably mediated by a β2-adrenergic mechanism, is partially responsible for the development of both peripheral and hepatic insulin resistance in animals infused with TNF.",
author = "Lang, {C. H.}",
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AB - 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 μg · h-1 · kg-1) was infused intravenously into chronically catheterized fasted rats for ~18 h. Before TNF, an infusion of either saline, propranolol (nonselective β-antagonist), atenolol (selective β1-antagonist), or phentolamine (α-antagonist) was started and continued throughout the experimental protocol. Infusion of either the α- or β-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 β-adrenergic stimulation, probably mediated by a β2-adrenergic mechanism, is partially responsible for the development of both peripheral and hepatic insulin resistance in animals infused with TNF.

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