Receptor Intestinal Del Gusto

J Physiol 582.1 (2007) pp 379–392

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Sweet taste receptors in rat small intestine stimulate glucose absorption through apical GLUT2
Oliver J. Mace, Julie Affleck, Nick Patel and George L. Kellett
Department of Biology (Area 3), University of York, York YO10 5YW, UK

Natural sugars and artificial sweeteners are sensed by receptors in taste buds. T2R bitter and T1R sweet taste receptorsare coupled through G-proteins, α-gustducin and transducin, to activate phospholipase C β2 and increase intracellular calcium concentration. Intestinal brush cells or solitary chemosensory cells (SCCs) have a structure similar to lingual taste cells and strongly express α-gustducin. It has therefore been suggested over the last decade that brush cells may participate in sugar sensing by a mechanismanalogous to that in taste buds. We provide here functional evidence for an intestinal sensing system based on lingual taste receptors. Western blotting and immunocytochemistry revealed that all T1R members are expressed in rat jejunum at strategic locations including Paneth cells, SCCs or the apical membrane of enterocytes; T1Rs are colocalized with each other and with α-gustducin, transducin orphospholipase C β2 to different extents. Intestinal glucose absorption consists of two components: one is classical active Na+ –glucose cotransport, the other is the diffusive apical GLUT2 pathway. Artificial sweeteners increase glucose absorption in the order acesulfame potassium ∼ sucralose > saccharin, in parallel with their ability to increase intracellular calcium concentration. Stimulationoccurs within minutes by an increase in apical GLUT2, which correlates with reciprocal regulation of T1R2, T1R3 and α-gustducin versus T1R1, transducin and phospholipase C β2. Our observation that artificial sweeteners are nutritionally active, because they can signal to a functional taste reception system to increase sugar absorption during a meal, has wide implications for nutrient sensing andnutrition in the treatment of obesity and diabetes.
(Received 22 February 2007; accepted after revision 10 May 2007; first published online 10 May 2007) Corresponding author: G. L. Kellett: Department of Biology (Area 3), University of York, York YO10 5YW, UK. Email: glk1@york.ac.uk

Intestinal glucose absorption occurs either via the classical pathway of active transport mediated by the Na+–glucose cotransporter SGLT1, or the apical GLUT2 pathway, which at high concentrations of sugar can be 3- to 5-times greater than by SGLT1. The apical GLUT2 pathway is mediated by glucose-induced insertion of GLUT2 into the apical membrane, thereby providing a cooperative mechanism by which glucose absorptive capacity is rapidly and precisely matched to dietary intake immediately after a meal (Kellett &Helliwell, 2000; Helliwell et al. 2000a,b; Kellett, 2001; Kellett & Brot-Laroche, 2005). Apical GLUT2 also provides a pathway of fructose entry in addition to that by GLUT5. The apical GLUT2 pathway is conserved in species from insects (Caccia et al. 2005, 2007) to humans (Kwon et al. 2006). It is abolished in GLUT2-null mice (Gouyon et al. 2003) and is regulated by experimental diabetes (Corpe etal. 1996), entero-endocrine sensing through glucagon like peptide (GLP-2) (Au et al. 2002), energy sensing by activated protein kinase (AMPK) (Walker et al. 2004), refeeding after starvation (Habold et al. 2005), long-term dietary carbohydrate intake (Gouyon et al. 2003) and
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development (Baba et al. 2005). Two signals mediate the regulation of the apical GLUT2 pathway by glucose. One isdietary Ca2+ : thus depolarization of the apical membrane by transport of glucose through SGLT1 stimulates Ca2+ entry via the L-type channel Cav 1.3 to cause contraction of the terminal web, which is essential for insertion (Morgan et al. 2003, 2007; Mace et al. 2007). However, little insertion occurs at low glucose concentrations (20 mm), even when the entry of Ca2+ is strongly stimulated; a...