Lipopolysaccharide alters suckling rat liver glycogenolysis.
Gram-negative sepsis/septic shock in the newborn continues to be a major medical problem, causing high mortality. Hyperglycemia followed by hypoglycemia is a common symptom in endotoxic shock. However, the mechanism of newborn glucoregulatory response to endotoxin has not been well understood. Paradoxically, monocyte-phagocytes can contribute to shock by overwhelming secretion of cytokines and also host defense by detoxifying endotoxin. Since monocyte-phagocyte function is immature in the newborn, this study was performed to evaluate Kupffer cell's role in liver glycogenolysis during endotoxic shock. Endotoxin (LPS) induced hyperglycemia in 10-day-old rats, and increased net glucose output in the isolated perfused liver. 1) Cytarabine decreased Kupffer cell function (decreased hepatic colloid carbon uptake) and blunted LPS-increased liver net glucose output in the Cytarabine + LPS-treated group (104 +/- 4 vs. 146 +/- 3 micrograms/min/g wet liver in the LPS-treated group: P < .001). 2) Indomethacin (IND) suppressed LPS-induced liver net glucose output in the LPS + IND-treated group (133 +/- 5 vs. 146 +/- 3 micrograms/min/g wet liver, P < .05). Thus, prostaglandins were suggested to contribute to glycogenolysis in the 10-day-old rat liver. 3) Phorbol 12-myristate 13-acetate (PMA) increased liver net glucose output (166 +/- 4 micrograms/min/g wet liver), and H-7, a protein kinase C inhibitor, blunted PMA-induced liver glucose output (140 +/- 2 micrograms/min/g wet liver, P < .05). H-7 enhanced LPS-induced liver net glucose output (196 +/- 9 micrograms/min/g wet liver, P < .01). Therefore, protein kinase C may not be the dominant cell signaling system for LPS stimulation in suckling rat Kupffer cells.
Goto
M
M
Department of Pediatrics, Stritch School of Medicine, Loyola University of Chicago, Maywood, IL 60153.
Zeller
W P
WP
Picken
M
M
Goto
M P
MP
Hurley
R M
RM
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D000831:Animals, Newborn; D003561:Cytarabine / Q000494:pharmacology; D004195:Disease Models, Animal; D006003:Glycogen / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D007728:Kupffer Cells / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012772:Shock, Septic / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D007546:Isoquinolines; D008070:Lipopolysaccharides; D010879:Piperazines; D003561:Cytarabine; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D006003:Glycogen; D013755:Tetradecanoylphorbol Acetate; D007213:Indomethacin