A diet-based Drosophila melanogaster model for the in vivo pharmacological evaluation of α-glucosidase inhibitors

The intestinal α-glucosidases maltase and sucrase break down the dietary disaccharides maltose and sucrose respectively into their monosaccharides for absorption by the body. These enzymes are therefore drug targets for hyperglycaemia-associated metabolic diseases. Here, we tested whether the fruit fly Drosophila melanogaster is a suitable in vivo model for evaluating the efficacy, specificity and tolerability of α-glucosidase inhibitors. To this end, we fed flies with different obesity-inducing high-sugar diets based on glucose, fructose, maltose and sucrose, respectively. The different types of dietary sugar allow the distinction between processes that require maltase or sucrase activity and those that are not related to α-glucosidase activity. Accordingly, administration of the established general α-glucosidase inhibitor acarbose reduced the triacylglyceride levels only in disaccharide-based diets. This was associated with a delayed larval development, a shortened lifespan and reduced spontaneous locomotor activity. Similar effects were not observed with monosaccharide-based diets. We conclude that acarbose is effective, selective, and well tolerated by the fly. By applying the same method approach, the root bark of the African mulberry Morus mesozygia was proved to be a potent in vivo inhibitor of maltase without side effects on the development and lifespan of D. melanogaster . We suggest that this convenient diet-based in vivo model is valuable even via non-invasive methods for evaluating novel drugs and bioactives with α-glucosidase inhibitory activity. • In the fruit fly model, α-glucosidase inhibitor specificity can be tested in vivo by selected dietary disaccharide types. • Monosaccharide-based diets are suitable to evaluate side effects of α-glucosidase inhibitors in the D. melanogaster model. • · Fat content, development, activity and lifespan of fruit flies are parameters to study α-glucosidase inhibitor efficacy.