The
retinoid X receptor agonists (rexinoids)
LG 100268 and
LG 100324 caused a reduction in the food intake of obese Zucker rats relative to controls and to rats receiving
BRL 49653. The two rexinoids also produced a marked decrease in the
body weight gain, whereas the growth rate of rats treated with
BRL 49653 tended to increase. Both rexinoids and
BRL 49653 reduced the plasma
insulin concentration of fed rats.
LG 100268 and
LG 100324 also significantly lowered
blood glucose concentrations after 1 week of treatment. The 5 h fasted plasma
insulin concentration was significantly lower in the rexinoid-treated groups and the terminal
insulin level (at the end of the clamp) tended to be lower in all treated groups compared with animals given the dosing vehicle. However, pancreatic
insulin content was not affected by any of the treatments. Under euglycaemic-hyperinsulinaemic clamp conditions, there were no significant differences in the rate of hepatic
glucose output and whole body
glucose disposal, except that, in experiment 1,
BRL 49653 caused significant increase in the
glucose infusion rate and muscle
glucose utilization. In experiment 2, a similar
glucose infusion rate to the controls was achieved in all treatment groups but the steady-state
insulin concentration in the treated animals was only about 50% of that in the control animals, despite the fact that all rats received a similar
insulin infusion concentration. This suggests that both the rexinoids and
BRL 49653 increased
insulin clearance.
CONCLUSIONS: