Attenuation of glucose metabolic changes resulting from TNF-alpha administration by adrenergic blockade.
Administration of tumor necrosis factor (TNF-alpha) increases whole body glucose kinetics and stimulates in vivo glucose uptake by several tissues. Because circulating catecholamines are also increased after TNF-alpha administration, the present study was conducted to examine the potential role of the adrenergic system in eliciting these changes. Rats given 150 micrograms TNF-alpha/kg by intravenous infusion over a 30-min period exhibited an increased rate of glucose appearance (glucose Ra). Combined alpha- and beta-adrenergic blockade (phentolamine and propranolol infusion) prevented the TNF-alpha-induced increase in glucose Ra without influencing plasma glucagon or corticosterone levels. TNF-alpha infusion also increased in vivo glucose utilization (Rg), measured with 2-deoxy-[14C]glucose, in spleen (86%), liver (80%), skin (47%), ileum (71%), lung (53%), and heart (112%). Adrenergic blockade prevented the tissue Rg increase in the spleen, liver, and skin; partially reduced it in the ileum; but did not abrogate it in the lung or heart. The effect of blockade was primarily due to inhibition of the TNF-alpha-induced increase in hepatic glucose output. Whereas the adrenergic system plays a major role on the effect of TNF-alpha on whole body glucose production, its importance in directly mediating TNF-alpha's effect on tissue glucose uptake is minimal.
Bagby
G J
GJ
Department of Physiology, Louisiana State University Medical Center, New Orleans 70112.
Lang
C H
CH
Skrepnik
N
N
Spitzer
J J
JJ
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D005947:Glucose / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D009994:Osmolar Concentration; D051381:Rats; D011919:Rats, Inbred Strains; D013565:Sympatholytics / Q000494:pharmacology*; D014018:Tissue Distribution; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*
D001786:Blood Glucose; D013565:Sympatholytics; D014409:Tumor Necrosis Factor-alpha; D005947:Glucose