Comparative hypoglycemic and hypoketonemic effects of tolbutamide and glypentide in rat

Abstract

Fed and 24 h fasted rats were treated by stomach tube with different doses of either tolbutamide or gluypentide and they were compared with controls treated with placebo. At low doses glypentide was ten times more effective as hypoglycemic agent than tolbultamide whereas it was only twice as effective in the fasted rats. Supramaximal doses of either drug produced the same effect decreasing blood glucose levels. Both drugs were able to decrease the rise of blood ketones in fasted rats, but the comparative effect was not parallel to the one observed on glycemia and not proportional to the doses used. The different responses are interpreted as function of the hypoglycemic effect, which would be mainly mediated through the insulinotropic action of these drugs, while the hypoketonemic would be the result of both their insulinotropic effect and their direct action on lipolysis and ketogenesis.