title: Sugar sensing by enterocytes combines polarity, membrane bound detectors and sugar metabolism.
abstract: Sugar consumption and subsequent sugar metabolism are known to regulate the expression of genes involved in intestinal sugar absorption and delivery. Here we investigate the hypothesis that sugar-sensing detectors in membranes facing the intestinal lumen or the bloodstream can also modulate intestinal sugar absorption. We used wild-type and GLUT2-null mice, to show that dietary sugars stimulate the expression of sucrase-isomaltase (SI) and L-pyruvate kinase (L-PK) by GLUT2-dependent mechanisms, whereas the expression of GLUT5 and SGLT1, did not rely on the presence of GLUT2. By providing sugar metabolites, sugar transporters, including GLUT2, fuelled a sensing pathway. In Caco2/TC7 enterocytes, we could disconnect the sensing triggered by detector from that produced by metabolism, and found that GLUT2 generated a metabolism-independent pathway to stimulate the expression of SI and L-PK. In cultured enterocytes, both apical and basolateral fructose could increase the expression of GLUT5, conversely, basolateral sugar administration could stimulate the expression of GLUT2. Finally, we located the sweet-taste receptors T1R3 and T1R2 in plasma membranes, and we measured their cognate G alpha Gustducin mRNA levels. Furthermore, we showed that a T1R3 inhibitor altered the fructose-induced expression of SGLT1, GLUT5, and L-PK. Intestinal gene expression is thus controlled by a combination of at least three sugar-signaling pathways triggered by sugar metabolites and membrane sugar receptors that, according to membrane location, determine sugar-sensing polarity. This provides a rationale for how intestine adapts sugar delivery to blood and dietary sugar provision.
authors.affiliation: INSERM, UMR S 872, Centre de Recherche des Cordeliers, Paris, France. mlegall@bhdc.jussieu.fr
authors.forename: Maude
authors.initials: M
authors.lastname: Le Gall
authors.forename: Vanessa
authors.initials: V
authors.lastname: Tobin
authors.forename: Emilie
authors.initials: E
authors.lastname: Stolarczyk
authors.forename: Véronique
authors.initials: V
authors.lastname: Dalet
authors.forename: Armelle
authors.initials: A
authors.lastname: Leturque
authors.forename: Edith
authors.initials: E
authors.lastname: Brot-Laroche
mesh_terms: D000818:Animals; D018938:Caco-2 Cells; D016764:Cell Polarity; D003001:Cloning, Molecular; D020895:Enterocytes / Q000378:metabolism*; D005632:Fructose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D051273:Glucose Transporter Type 2 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051296:Glucose Transporter Type 5 / Q000235:genetics / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006601:Hexoses / Q000378:metabolism*; D006801:Humans; D007583:Jejunum / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009004:Monosaccharide Transport Proteins / Q000235:genetics / Q000378:metabolism*; D009834:Oligo-1,6-Glucosidase / Q000235:genetics; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D051269:Sodium-Glucose Transporter 1 / Q000235:genetics / Q000378:metabolism; D013393:Sucrase / Q000235:genetics; D013395:Sucrose / Q000378:metabolism*; D013549:Sweetening Agents / Q000378:metabolism*; D014162:Transfection