Insulin-like action of endotoxin: antagonism by steroidal and nonsteroidal anti-inflammatory agents

Circ Shock. 1981;8(5):573-83.

Abstract

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.

MeSH terms

  • Adipose Tissue / metabolism
  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Dexamethasone / pharmacology
  • Endotoxins / pharmacology*
  • Epididymis / metabolism
  • Glucose / metabolism
  • Indomethacin / pharmacology
  • Insulin / pharmacology*
  • Male
  • Methylprednisolone / pharmacology
  • Rats
  • Rats, Inbred Strains
  • Steroids / pharmacology*

Substances

  • Anti-Inflammatory Agents
  • Endotoxins
  • Insulin
  • Steroids
  • Dexamethasone
  • Glucose
  • Methylprednisolone
  • Indomethacin