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Two daily administrations of glibenclamide or nateglinide for three days to normal rats fail to affect the glycemic and insulinemic responses to glucose of the same antidiabetics agents

par Oguzhan, BERRIN ;Jurysta, Cédric ;Jijakli, Hassan ;Courtois, Philippe ;Sener, Abdullah ;Malaisse, Willy
Référence Fundamental & clinical pharmacology, 19, 3, page (402)
Publication Publié, 2004

Article révisé par les pairs

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Résumé :

Glibenclamide and nateglinide are two antidiabetic agents belonging, respectively, to the sulfonylurea and meglitinide family. The major aim of the present study was to investigate whether the prior administration twice daily for three days of these agents to normal rats affects the plasma D-glucose and insulin responses to either enteral D-glucose or the same diabetic agents. Glibenclamide (1.0 μg/g body wt.) or nateglinide (50.0 μg/g body wt.) was given by gastric tubing mixed with 2.0 ml of a 0.5 % solution of carboxymethylcellulose. D-glucose (15 μmol/g body wt.) was administered as a 3.5 M solution. Except for a lower plasma D-glucose concentration in the glibenclamide group, no significant difference was found between the three groups of rats on the morning of the fourth day. Likewise, the plasma D-glucose and insulin responses to either D-glucose or the antidiabetic agents were not significantly different in control, glibenclamide- and nateglinide-pretreated rats. The time course for the increase in plasma insulin concentration and lowering of plasma D-glucose concentration was characterized by earlier peak and nadir values, respectively, in the rats receiving nateglinide rather than glibenclamide. These findings indicate that, in normal rats, the secretory responsiveness of insulin-producing cells and glucose homeostasis are not significantly affected by mid-term administration of either glibenclamide or nateglinide, despite the different time course of their effects on both insulin secretion and glycemia.