title: Intestinal glucose-dependent expression of glucose-6-phosphatase: involvement of the aryl receptor nuclear translocator transcription factor.
abstract: Glucose-6-phosphatase (G6Pase) catalyzes the release of glucose from glucose 6-phosphate. This enzyme was mainly studied in the liver, but while detected in the small intestine little is known about the regulation of its intestinal expression. This study describes the mechanisms of the glucose-dependent regulation of G6Pase expression in intestinal cells. Results obtained in vivo and in Caco-2/TC7 enterocytes showed that glucose increases the G6Pase mRNA level. In Caco-2/TC7 cells, glucose stabilized G6Pase mRNA and activated the transcription of the gene, meaning that glucose-dependent G6Pase expression involved both transcriptional and post-transcriptional mechanisms. Reporter-gene studies showed that, although the -299/+57 region of the human G6Pase promoter was sufficient to trigger the glucose response in the hepatoma cell line HepG2, the -1157/-1133 fragment was required for maximal activation of glucose-6-phosphatase gene transcription in Caco-2/TC7 cells. This fragment binds the aryl receptor nuclear translocator (ARNT), cAMP-responsive element-binding protein, and upstream stimulatory factor transcription factors. The DNA binding activity of these transcription factors was increased in nuclear extracts of differentiated cells from the intestinal villus of mice fed sugar-rich diets as compared with mice fed a no-sugar diet. A direct implication of ARNT in the activation of G6Pase gene transcription by glucose has been observed in Caco-2/TC7 cells using RNA interference experiments. These results support a physiological role for G6Pase in the control of nutrient absorption in the small intestine.
authors.affiliation: INSERM UMR 505, Université Pierre et Marie Curie, Paris, France. veronique.carriere-u505@bhdc.jussieu.fr
authors.forename: Véronique
authors.initials: V
authors.lastname: Carrière
authors.forename: Maude
authors.initials: M
authors.lastname: Le Gall
authors.forename: Florence
authors.initials: F
authors.lastname: Gouyon-Saumande
authors.forename: Dieter
authors.initials: D
authors.lastname: Schmoll
authors.forename: Edith
authors.initials: E
authors.lastname: Brot-Laroche
authors.forename: Valérie
authors.initials: V
authors.lastname: Chauffeton
authors.forename: Jean
authors.initials: J
authors.lastname: Chambaz
authors.forename: Monique
authors.initials: M
authors.lastname: Rousset
mesh_terms: D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D018938:Caco-2 Cells; D002460:Cell Line; D004247:DNA / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D017930:Genes, Reporter; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D005952:Glucose-6-Phosphatase / Q000235:genetics*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000378:metabolism; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D020871:RNA Stability / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects
chemical_list: C497396:ARNT protein, human; C497397:Arnt protein, mouse; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D014157:Transcription Factors; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D004247:DNA; D005952:Glucose-6-Phosphatase; D005947:Glucose