Sugar sensing by enterocytes combines polarity, membrane bound detectors and sugar metabolism.
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.
Le Gall
Maude
M
INSERM, UMR S 872, Centre de Recherche des Cordeliers, Paris, France. mlegall@bhdc.jussieu.fr
Tobin
Vanessa
V
Stolarczyk
Emilie
E
Dalet
Véronique
V
Leturque
Armelle
A
Brot-Laroche
Edith
E
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