Effects of trecadrine, a beta 3-adrenergic agonist, on intestinal absorption of D-galactose and disaccharidase activities in three physiopathological models.

ABSTRACT

Impairments in intestinal absorptive and digestive processes have been described in several pathophysiological situations, such as in drug-induced diabetes, obesity and hypercholesterolaemia. Furthermore, there is evidence for the occurrence of beta 3-adrenoceptors in multiple regions of the gastrointestinal tract, but there are no data concerning their possible involvement on jejunal and ileal digestive and absorptive functions. In this work, we have measured the modifications of selective intestinal absorption and disaccharidase activities in alloxan-induced diabetic and in diet-induced obese and hypercholesterolaemic Wistar rats. The action of a beta 3-adrenergic agonist (Trecadrine) with hypoglycaemic and lipolytic properties on those gastrointestinal functions has been studied. Increases in the galactose uptake by intestinal rings and in both sucrase and maltase activities were found in diabetic rats. The results obtained after Trecadrine administration to diabetic rats led to an improvement of the altered values. On the other hand, our data show a decrease in sugar absorption and in disaccharidase activities in both obese and hypercholesterolaemic groups, probably related to the low carbohydrate and high fat content of these diets. An amelioration in sucrase activity was observed after treatment with Trecadrine. Finally, Trecadrine administration to control animals significantly inhibited galactose intestinal absorption, which was independently confirmed by additional in-vitro studies. Overall, these results could be attributed not only to an improvement in the pathophysiological condition (diabetes, obesity and hypercholesterolaemia), but also to a direct effect of the beta 3-adrenergic agonist on the intestinal absorption processes.