Abstract
BackgroundThe 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.AimsTo study the direct model of intestinal sugar transport using CaCo-2 cells, a well-established in vitro model of the human enterocyte.MethodsUptake 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.ResultsIn 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.ConclusionsIn 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.
Highlights
Carbohydrate digestion and absorption occurs primarily in the small intestine (SI)
Artificial Sweeteners and Small Intestinal Sugar Transport increased glucose transport in cells exposed to glucose/fructose
We found no evidence of a functional heterodimeric sweet taste receptor, T1R2/3 in CaCo-2 cells
Summary
Carbohydrate digestion and absorption occurs primarily in the small intestine (SI). In the SI, sugar oligomers and disaccharides are broken down into monosaccharides by enzymes such as sucrase-isomaltase that are expressed on the apical membrane of the enterocyte. In order to match assimilation capacity with the luminal carbohydrate load the digestive and transporter mechanisms are tightly regulated: without tight regulation nutrient malabsorption would occur. In rats, when luminal jejunal glucose levels increase, the sweet taste receptor T1R2/3 on the apical membrane of the enterocyte becomes activated, resulting in a rapid and reversible insertion of GLUT2 into the apical membrane which enhances small intestinal sugar transport capacity [4,5]. 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
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