Insulin action and binding in adipocytes exposed to endotoxin in vitro and in vivo

We investigated in vitro and in vivo effects of endotoxin on glucose oxidation and insulin binding in rat adipocytes. Exposure of adipocytes to endotoxin (500 micrograms/ml) in vitro resulted in 48% increase in basal glucose oxidation after 30 minutes, 63% and 65% increase after 90 and 150 minutes, respectively. Adipocytes from rats injected 6 hours previously with endotoxin IV (2 mg/100 gm) also showed elevated (42%) basal glucose oxidation. Both the absolute levels of stimulation and sensitivity to insulin stimulation were less than in control cells. A tendency for higher insulin binding affinity at low ambient insulin concentrations was noted. At higher insulin concentrations this difference disappeared. Our results demonstrate an insulin-like effect of endotoxin, as well as perturbation by endotoxin of insulin action at the cellular level. Changes in receptor affinity are also suggested, implying that the insulin receptor may be a site for modulation of target cell sensitivity in endotoxemia.