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 naloxone 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 Escherichia coli endotoxin 0.25 mg in saline; 5 were given a naloxone infusion (0.4 ml of 0.04 mg/ml for the first half hour and continued at a rate of 0.4 ml/hour for a total of 80 minutes) starting 10 minutes before 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 after 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 substances rose significantly 70 minutes after the injection of endotoxin compared 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) pmol/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.

CONCLUSIONS

The rise in glucagon and insulin concentrations after endotoxin infusions may be partly mediated by opioids. Naloxone in the dose given did not abolish the increase in glucagon after endotoxin. The high glucagon:insulin ratio after both endotoxin alone and endotoxin plus naloxone may be important in the aetiology of the hyperglycaemia seen.