Interleukin 6 stimulates hepatic glucose release from prelabeled glycogen pools.
Cytokines, derived from a wide variety of cell types, are now believed to initiate many of the physiological responses accompanying the inflammatory phase that follows either Gram-negative septicemia or thermal injury. Because hypoglycemia (after endotoxic challenge) and hyperglycemia (after thermal injury) represent well-characterized responses to these injuries, we sought to determine whether hepatic glycogen metabolism could be altered by specific cytokines. Cultured adult rat hepatocytes were prelabeled with [14C]glucose for 24 h, a procedure that resulted in the labeling of hepatic glycogen pools that subsequently could be depleted (with concomitant [14C]glucose release) by either glucagon or norepinephrine. After the addition of a highly concentrated human monocyte-conditioned medium (MCM) or various cytokines to these prelabeled cells, [14C]glucose release was stimulated by MCM and recombinant human interleukin 6 (IL-6) but was not stimulated by other cytokines tested. Furthermore, only antisera to IL-6 were capable of reducing the glucose-releasing factor activity found in MCM. These data therefore suggest a novel glucoregulatory role for IL-6.
Ritchie
D G
DG
Shriners Burns Institute, Galveston, Texas.
D000818:Animals; D002250:Carbon Radioisotopes; D002478:Cells, Cultured; D003470:Culture Media; D005934:Glucagon / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology*; D007378:Interleukins / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D009000:Monocytes / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology; D011865:Radioisotope Dilution Technique; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000494:pharmacology; D013696:Temperature; D014316:Tritium; D014357:Trypsin / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D002250:Carbon Radioisotopes; D003470:Culture Media; D015850:Interleukin-6; D007378:Interleukins; D008112:Liver Glycogen; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D014316:Tritium; D007371:Interferon-gamma; D005934:Glucagon; D014357:Trypsin; D005947:Glucose; D009638:Norepinephrine