Insulin-like action of endotoxin: antagonism by steroidal and nonsteroidal anti-inflammatory agents.
Studies were undertaken to evaluate the direct insulin-like action of S enteritidis endotoxin on glucose oxidation in the rat epididymal fat pad and to assess antagonism by steroidal and nonsteroidal anti-inflammatory agents. In vitro administration of endotoxin at concentrations of 500, 100, 50, and 10 micrograms/ml significantly increased adipose tissue glucose oxidation by 115, 92, 55, and 32%, respectively. Exposure of the fat pads to endotoxin (100 microgram/ml) for timed incubations of 120 to 5 min, all produced significant increments in glucose oxidation. The insulin-like action of endotoxin was significantly less in Ca2+ free-KRB plus EGTA. Cotreatment of the fat pads with endotoxin and the steroidal anti-inflammatory agents, dexamethasone and methylprednisolone, as well as the nonsteroidal anti-inflammatory agent, indomethacin, significantly antagonized endotoxin-stimulated glucose oxidation. Dexamethasone antagonism was not significant if it was added after endotoxin treatment. Testosterone, a steroid with no anti-inflammatory activity, did not antagonize endotoxin's insulin-like action. The data provide further evidence of the direct insulin-like action of endotoxin and suggest that the protective effect of dexamethasone, methylprednisolone, and indomethacin may be due, in part, to a direct antagonism of endotoxin at the tissue level.
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D003907:Dexamethasone / Q000494:pharmacology; D004731:Endotoxins / Q000494:pharmacology*; D004822:Epididymis / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D007213:Indomethacin / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013256:Steroids / Q000494:pharmacology*
D000893:Anti-Inflammatory Agents; D004731:Endotoxins; D007328:Insulin; D013256:Steroids; D003907:Dexamethasone; D005947:Glucose; D008775:Methylprednisolone; D007213:Indomethacin