Insulin Action and Binding Kinetics in Adipocytes Exposed to Endotoxin 'in vitro'and 'in vivo'.

摘要

The in vitro and in vivo effects of E. coli endotoxin were investigated on rat adipocytes in terms of oxidation of U-14C-glucose and insulin binding kinetics. Isolated adipocytes exposed to endotoxin (500 microgram/ml) in vitro demonstrated a 48% increase in basal glucose oxidation with 30 minutes of exposure and 63% and 65% increase if exposed for 90 and 150 minutes, respectively. Consistent alterations were not found in insulin binding to cells exposed for up to 90 minutes to endotoxin (20 or 500 microgram/ml) in vitro. Adipocytes from rats injected with endotoxin i.v. (2 mg/100 g body weight) and killed 6 hours later also showed an elevation (42%) in basal glucose oxidation. Incremental insulin stimulation as well as the absolute levels of stimulation reached by these cells were less than in controls. Insulin binding experiments with cells from endotoxin injected rats showed a tendency for higher binding affinity at low ambient insulin concentrations (low receptor occupancy). At higher insulin concentrations (high receptor occupancy) this difference diminished. The results demonstrate an insulin like effect of endotoxin, as well as perturbation by endotoxin of insulin action at the cellular level. The study also suggests changes in receptor affinity, thus implying that the insulin receptor may be a site for modulation of target cell sensitivity in endotoxemia.