title: Acute Effects of Sugars and Artificial Sweeteners on Small Intestinal Sugar Transport: A Study Using CaCo-2 Cells As an In Vitro Model of the Human Enterocyte.
abstract: BACKGROUND
  The gastrointestinal tract is responsible for the assimilation of nutrients and plays a key role in the regulation of nutrient metabolism and energy balance. The molecular mechanisms by which intestinal sugar transport are regulated are controversial. Based on rodent studies, two models currently exist that involve activation of the sweet-taste receptor, T1R2/3: an indirect model, whereby luminal carbohydrates activate T1R2/3 expressed on enteroendocrine cells, resulting in the release of gut peptides which in turn regulate enterocyte sugar transport capacity; and a direct model, whereby T1R2/3 expressed on the enterocyte regulates enterocyte function.
  
  
  OBJECTIVE
  To study the direct model of intestinal sugar transport using CaCo-2 cells, a well-established in vitro model of the human enterocyte.
  
  
  METHODS
  Uptake of 10mM 14C D-Glucose and D-Fructose into confluent CaCo-2/TC7 cells was assessed following 3hr preincubation with sugars and artificial sweeteners in the presence and absence of the sweet taste receptor inhibitor, lactisole. Expression of the intestinal sugar transporters and sweet-taste receptors were also determined by RT-PCR.
  
  
  RESULTS
  In response to short term changes in extracellular glucose and glucose/fructose concentrations (2.5mM to 75mM) carrier-mediated sugar uptake mediated by SGLT1 and/or the facilitative hexose transporters (GLUT1,2,3 and 5) was increased. Lactisole and artificial sweeteners had no effect on sugar transport regulated by glucose alone; however, lactisole increased glucose transport in cells exposed to glucose/fructose. RT-PCR revealed Tas1r3 and SGLT3 gene expression in CaCo-2/TC7 cells, but not Tas1r2.
  
  
  CONCLUSIONS
  In the short term, enterocyte sugar transport activities respond directly to extracellular glucose levels, but not fructose or artificial sweeteners. We found no evidence of a functional heterodimeric sweet taste receptor, T1R2/3 in CaCo-2 cells. However, when glucose/fructose is administered together there is an inhibitory effect on glucose transport possibly mediated by T1R3.
authors.affiliation: Diet and Cardiovascular Health Group, Diabetes and Nutritional Sciences Division, King's College London, London, United Kingdom.
authors.forename: Patrick
authors.initials: P
authors.lastname: O'Brien
authors.affiliation: Diet and Cardiovascular Health Group, Diabetes and Nutritional Sciences Division, King's College London, London, United Kingdom.
authors.forename: Christopher Peter
authors.identifier: http://orcid.org/0000-0003-1994-8312
authors.initials: CP
authors.lastname: Corpe
mesh_terms: D001555:Benzene Derivatives / Q000494:pharmacology; D001692:Biological Transport; D018938:Caco-2 Cells; D020895:Enterocytes / Q000187:drug effects / Q000378:metabolism*; D005632:Fructose / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D051246:Glucose Transport Proteins, Facilitative / Q000235:genetics; D006801:Humans; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D051269:Sodium-Glucose Transporter 1 / Q000235:genetics; D013549:Sweetening Agents / Q000378:metabolism*
chemical_list: D001555:Benzene Derivatives; D051246:Glucose Transport Proteins, Facilitative; D043562:Receptors, G-Protein-Coupled; C495674:SLC5A1 protein, human; D051269:Sodium-Glucose Transporter 1; D013549:Sweetening Agents; C431926:taste receptors, type 1; D005632:Fructose; D005947:Glucose; C495512:lactisole