EFFECTS OF NALOXONE ON GLUCAGON AND INSULIN CONCENTRATIONS AFTER INJECTION OF ENDOTOXIN IN RATS

Objective: To find out how infusions of endotoxin and endotoxin plus n aloxone affected glucose, glucagon, and insulin concentrations in rats . Design: Random control study. Setting: University hospital, Norway. Material: 27 Male Wistar rats. Interventions: 8 Rats were given Escher ichia coil endotoxin 0.25 mg in saline; 5 were given a naloxone infusi on (0.4 ml of 0.04 mg/ml for the first half hour and continued at a ra te of 0.4 ml/hour for a total of 80 minutes) starting 10 minutes befor e the same dose of endotoxin; 6 were given saline alone for 70 minutes , and 8 saline alone for 10 minutes. Blood was taken for analysis afte r 70 minutes in the first three groups and at the end of the infusion in the 10 minute group. Main outcome measures: Serum concentrations of glucose, glucagon, and insulin compared with baseline (10 min group). Results: Median (interquartile) concentrations of all three substance s rose significantly 70 minutes after the injection of endotoxin compa red to basal values: 9.8 (8.2-10.9) compared with 6.0 (4.8-7.5) mmol/l for glucose (p < 0.01); 53.1 (44.6-56.0) compared with 3.6 (3.1-5.1) ng/l for glucagon; and 39.4 (38-50.4) compared with 16.7 (11.2-25.5) p mol/l for insulin. When naloxone was combined with endotoxin glucagon and insulin concentrations were significantly lower: 24.3 (23.9-37.5) ng/l (p < 0.01), and 30.6 (24.5-31.6 pmol/l (p < 0.05), respectively. The concentration of glucose in venous blood was unchanged. Conclusion s: The rise in glucagon and insulin concentrations after endotoxin inf usions may be partly mediated by opioids. Naloxone in the dose given d id not abolish the increase in glucagon after endotoxin. The high gluc agon:insulin ratio after both endotoxin alone and endotoxin plus nalox one may be important in the aetiology of the hyperglycaemia seen.