Nerveless and gutsy: intestinal nutrient sensing from invertebrates to humans

Abstract

The increasingly recognized role of gastrointestinal signals in the regulation of food intake, insulin production and peripheral nutrient storage has prompted a surge of interest in studying how the gastrointestinal tract senses and responds to nutritional information. Identification of metabolically important intestinal nutrient sensors could provide potential new drug targets for the treatment of diabetes, obesity and gastrointestinal disorders. From a more fundamental perspective, the study of intestinal chemosensation is revealing novel, non-neuronal modes of communication involving differentiated epithelial cells. It is also identifying signalling mechanisms downstream of not only canonical receptors but also nutrient transporters, thereby supporting a chemosensory role for "transceptors" in the intestine. This review describes known and proposed mechanisms of intestinal carbohydrate, protein and lipid sensing, best characterized in mammalian systems. It also highlights the potential of invertebrate model systems such as C. elegans and Drosophila melanogaster by summarizing known examples of molecular evolutionary conservation. Recently developed genetic tools in Drosophila, an emerging model system for the study of physiology and metabolism, allow the temporal, spatial and high-throughput manipulation of putative intestinal sensors. Hence, fruit flies may prove particularly suited to the study of the link between intestinal nutrient sensing and metabolic homeostasis.

Fig. 1

Three different modalities of intestinal nutrient sensing. (A) A taste receptor signals in EECs to affect incretin release, which, in turn, affects the expression or membrane availability of transporters in ECs. (B) Possible modes of nutrient-coupled electrogenic transport in EECs or ECs. (C) Possible mechanisms by which nutrient binding to metabolic transceptors leads to incretin release (EECs) or changes in gene expression in ECs. See text for details.