Insulin tolerance during endotoxic shock in 10-day-old rats

Purpose. The purpose was to investigate insulin tolerance during endotoxic shock in 10-day-old rats. Materials and Methods. [C-14]Deoxy-glucose (2DG) with or without insulin (1 unit/kg) was injected to 10-day-old and 6-week-old rats 3 h after an injec tion of endotoxin (lipopolysaccharide: LPS). Plasma concentrations of gluco se and 2DG: were serially measured for 45 min. Gluconeogenesis was measured in hepatocytes isolated from control and endotoxic 10-day-old rats to eval uate effects of insulin on gluconeogenesis. Results. In endotoxic 10-day-old rats, plasma glucose concentration at 45 m in was 48 +/- 3% (P < 0.05) of value at 0 min, and when insulin was injecte d with 2DG, it was 29 +/- 45 (P < 0.05) after insulin injection. Plasma 2DG disappearance was enhanced by insulin injection in the control (t(1/2) = 1 7.9 vs 20.5 min, P < 0.05), but not in the endotoxic rats (t(1/2) = 17.9 vs 18.4 min), indicating the presence of insulin tolerance in septic rats. In sulin decreased gluconeogenesis (P < 0.05) in hepatocytes from both control and endotoxic 10-day-old rats. In endotoxic 6-week-old rats, plasma glucose concentration was decreased to 46 +/- 10% at 45 min and further decreased to 38 +/- 4% (P < 0.05) by insu lin injection. Plasma 2DG disappearance was enhanced by insulin injection i n the control (t(1/2) = 11.8 VS 17.4 min, P < 0.05) and in the septic rats (t(1/2) = 14.8 VS 12.2 min). However, the enhancement of plasma 2DG disappe arance by insulin was less (P < 0.05) in the septic rats than in the contro l, confirming reports of other investigators which showed insulin tolerance in septic shock. Conclusion. Although hepatocytes from endotoxic rats retained insulin sensi tivity, insulin tolerance which was evaluated by 2DG; disappearance occurre d during septic shock in newborn rats. (C) 2000 Academic Press.