Endotoxin and fibrinogen degradation product-D have different actions on carbohydrate metabolism: role of Kupffer cells.
The effect of endotoxin-derived lipopolysaccharide (LPS) and fibrinogen degradation product D (FDPD) on oxygen consumption and glycogenolysis in the perfused rat liver was investigated. 1. Infusion of LPS (100 micrograms/ml) or FDPD (7 micrograms/ml) caused a rapid stimulation of oxygen uptake by the perfused liver of 10-12 mumol/g/h. 2. LPS also caused a transient increase in glucose and lactate release into the perfusion medium from endogenous glycogen; however, FDPD was without effect. 3. Destruction of Kupffer cells by GdCl3 pretreatment blocked the effects of LPS and FDPD on oxygen uptake and glycogenolysis. Further, LPS and FDPD had no effect on oxygen consumption by isolated hepatocytes. Therefore, it is concluded that Kupffer cells are involved in the increase of hepatic oxygen consumption and carbohydrate release caused by LPS, most likely via release of PGE2 and PGD2. Since FDPD increased oxygen but not carbohydrate release, it is concluded that it acts via stimulating the release of mediators distinct from those released following LPS infusion.
Department of Pharmacology, University of North Carolina at Chapel Hill, USA.
J
J
Mandl
C
C
Wall
I
I
Lerant
A
A
Falus
R
R
Machovich
R G
RG
Thurman
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D004731:Endotoxins / Q000494:pharmacology*; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000494:pharmacology*; D005682:Gadolinium / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism*; D007728:Kupffer Cells / Q000378:metabolism*; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley
D000893:Anti-Inflammatory Agents; D004731:Endotoxins; D005338:Fibrin Fibrinogen Degradation Products; D007773:Lactates; D008070:Lipopolysaccharides; D019344:Lactic Acid; D006003:Glycogen; D005682:Gadolinium; D005947:Glucose; C038958:gadolinium chloride