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

The purpose was to investigate insulin tolerance during endotoxic shock in 10-day-old rats.

[(14)C]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 injection of endotoxin (lipopolysaccharide: LPS). Plasma concentrations of glucose and 2DG were serially measured for 45 min. Gluconeogenesis was measured in hepatocytes isolated from control and endotoxic 10-day-old rats to evaluate effects of insulin on gluconeogenesis.

In endotoxic 10-day-old rats, plasma glucose concentration at 45 min was 48 +/- 3% (P < 0.05) of value at 0 min, and when insulin was injected with 2DG, it was 29 +/- 4% (P < 0.05) after insulin injection. Plasma 2DG disappearance was enhanced by insulin injection in the control (t(1/2) = 17.9 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. Insulin 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 insulin injection. Plasma 2DG disappearance was enhanced by insulin injection in 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 disappearance by insulin was less (P < 0.05) in the septic rats than in the control, confirming reports of other investigators which showed insulin tolerance in septic shock.

Although hepatocytes from endotoxic rats retained insulin sensitivity, insulin tolerance which was evaluated by 2DG disappearance occurred during septic shock in newborn rats.