title: Regulation of glucose metabolism after endotoxin and during infection is largely independent of endogenous tumor necrosis factor.
abstract: Increased hepatic glucose production and glucose utilization involving multiple tissues occur in response to administration of bacterial lipopolysaccharide (LPS) and are metabolic hallmarks of hypermetabolic sepsis. As a proximal mediator in the host response to infection-like challenges, tumor necrosis factor (TNF) may enhance glucose metabolism by directly interacting with cells or by initiating a cascade of events leading to changes in glucose production and utilization. To determine if endogenous TNF is an important mediator in LPS- or sepsis-induced changes in glucose metabolism, rats were pretreated with a neutralizing goat anti-TNF IgG antibody prior to intravenous LPS or subcutaneous live Escherichia coli administration. Whereas high levels of plasma TNF were observed in rats not pretreated with anti-TNF, TNF was not detected 90 min after LPS in rats receiving the antibody. Pretreatment with anti-TNF attenuated the increase in plasma lactate and glucagon levels in LPS-challenged rats but failed to ameliorate the LPS-induced hyperglycemia and increase in glucose rate of appearance (Ra). The LPS-stimulated increase of in vivo glucose metabolic rate (Rg) of examined tissues, measured with [14C]-2-deoxyglucose, was not altered by anti-TNF. Likewise, rats treated with anti-TNF prior to induction of hypermetabolic infection exhibited usual increases in whole-body glucose Ra and metabolic clearance rate. Although neutralizing TNF failed to prevent the sepsis-induced augmentation of Rg in any tissue examined, it reduced the increase in the lung (P < 0.05) and tended to decrease it in other barrier tissues as well as in the spleen.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Physiology, Louisiana State University Medical Center, New Orleans 70112.
authors.forename: G J
authors.initials: GJ
authors.lastname: Bagby
authors.forename: C H
authors.initials: CH
authors.lastname: Lang
authors.forename: N
authors.initials: N
authors.lastname: Skrepnik
authors.forename: G
authors.initials: G
authors.lastname: Golightly
authors.forename: J J
authors.initials: JJ
authors.lastname: Spitzer
mesh_terms: D000818:Animals; D004731:Endotoxins / Q000494:pharmacology*; D004927:Escherichia coli Infections / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000502:physiology*
chemical_list: D004731:Endotoxins; D007074:Immunoglobulin G; D014409:Tumor Necrosis Factor-alpha; D005947:Glucose