Insulin resistance and depressed gluconeogenic capability during early hyperglycemic sepsis.
The present study was performed to determine whether insulin resistance, independent of the prevailing hormonal milieu, occurs in the liver during sepsis. To determine this, sepsis was produced in rats by cecal ligation and puncture (CLP). Six hours later, when the rats were in the early hypermetabolic phase of sepsis, the livers were isolated and perfused with Krebs-HCO3 buffer using a nonrecirculating system. The effects of various concentrations of insulin on the gluconeogenic response to lactate and phenylephrine stimulation were determined. In the absence of insulin and phenylephrine, there was no difference in the rates of glucose production from lactate between septic and sham-operated rats. The gluconeogenic response to phenylephrine stimulation was, however, significantly depressed in the livers from septic rats. Addition of 50 microU insulin/ml resulted in an inhibition of the phenylephrine-stimulated glucose release from livers from sham-operated rats. This inhibition was maximal at 100 microU insulin/ml. In contrast, significant inhibition of phenylephrine-stimulated glucose release from livers from septic rats was only observed in the presence of 2,000 microU insulin/ml. These results demonstrate that even during the early, hypermetabolic phase of sepsis, depressed hormonally stimulated hepatic gluconeogenic capability occurs. In addition, livers from septic rats exhibited a resistance to the effects of insulin on gluconeogenesis. This resistance may account, at least in part, for accelerated gluconeogenesis in spite of hyperinsulinemia in early sepsis.
D000005:Abdomen; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005943:Gluconeogenesis; D007239:Infections / Q000503:physiopathology*; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects / Q000503:physiopathology*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats
D007328:Insulin; D010656:Phenylephrine