Taste and move: glucose and peptide transporters in the gastrointestinal tract

Nutrient transporters are integral membrane proteins responsible for uptake into enterocytes and release of nutrients into the circulation. Absorption of food breakdown products, such as fatty acids, monosaccharides or amino acids, requires high-capacity transporters. In the case of glucose, amino acids and peptides, the transporters are electrogenic in nature, coupling substrate flux to ion movement. While glucose absorption is mediated by the Na+-dependent SGLT1 protein, uptake of short-chain peptides is mediated by the H+-coupled PEPT1 protein. Interestingly, both transporters were recently shown to fulfil an additional role as intestinal 'sensors' in enteroendocrine cells, mediating the release of gastrointestinal peptide hormones into the circulation. Sensing of D-glucose and of di- and tripeptides is particularly relevant for the secretion of the incretins glucose-dependent insulinotrophic polypeptide and glucagon-like peptide 1 that promote insulin output from beta-cells and mediate beta-cell protection. In addition to these sensing pathways, a variety of G-protein-coupled receptors are involved in sensing of intestinal contents. D-Glucose is sensed not only by SGLT1 but also by the sweet taste receptor T1R2/3 expressed in enteroendocrine cells. Activation of T1R2/3 increases SGLT1 levels and intestinal glucose absorption. Although T1R2/3 ligands, such as artificial sweeteners, were shown to elicit incretin secretion from enteroendocrine cell lines or in vitro in tissue preparations, convincing data that this is also relevant in vivo are missing to date. However, there is growing interest in targeting intestinal sensory pathways, involving receptors but also the 'transceptors' PEPT1 and SGLT1, by use of drugs or food constituents to elicit the beneficial effects of incretins on the pancreas and metabolic control.