Understanding the mechanisms by which nutrients are absorbed in the gastrointestinal tract has been a subject of research for more than hundred years. In particular the absorption of monosaccharides as the quantitatively most important nutrient class attracted scientists from physiology, gastroenterology and more recently also from molecular biology and genetics. Absorption of short chain peptides in intact form represents the exception to the rule according to which only the monomers of the complex food constituents are absorbed into epithelial cells. With the cloning of the membrane proteins that mediate the influx of nutrients into epithelial cells in the 1990’s a new chapter was opened and numerous wonderful studies since then have been assessing the structure and functions of the proteins. However, there are still some very fundamental aspects that are not resolved. There is for example a controversial debate on whether intestinal glucose absorption at high luminal glucose concentrations involves a second transport system – such as GLUT2 – in addition to the electrogenic Na+-dependent transporter SGLT1. I shall be presenting studies in mice lacking SGLT1 or lacking the facilitated glucose transporter GLUT2 to determine whether GLUT2 contributes to overall glucose and/or fructose absorption. The latter is thought to be mediated by GLUT5 in apical membranes and is also thought to be the basis of fructose malabsorption which is not yet defined on a molecular or genetic basis. Most interestingly, as shown in humans, fructose malabsorption can be overcome when simultaneously glucose is provided although the mechanisms underlying this phenomenon are not known. Intestinal absorption of short chain peptides is mediated by the rheogenic transporter PEPT1. There is no disease associated with a malfunction of PEPT1. However, in inherited diseases of amino acid transport, such as Cystinuria or Hartnup disease, impaired intestinal amino acid absorption was shown to be compensated by uptake of the critical amino acids in peptide form via PEPT1. An interplay of SGLT1, GLUT2 and PEPT1 was proposed based on studies in rats to represent a network by which the intestine absorbs in a coordinated manner large quantities of nutrients that also represent an osmotic challenge. However, using the various transporter-deficient mouse strains we did not find any evidence that glucose and peptide transport processes are interconnected. What came as a surprise is the finding that both SGLT1 and PEPT1 as “classical” transporters have a second role and that is that of a sensor in enteroendocrine cells in the gut allowing luminal sensing for release of gastrointestinal peptide hormones, primarily of GIP and GLP1.