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Báo cáo khoa học: Glucose sensing in the intestinal epithelium

Dietary sugars regulate expression of the intestinal Na + / glucose cotransporter, SGLT1, inmany species.Using sheep intestine as a model, we showed that lumenal monosaccha-rides, both metabolisable and nonmetabolisable, regulate SGLT1 expression. This regulation occurs not only at the level of transcription, but also at the post-transcriptional level. Introduction of D-glucose andsome D-glucose ana-logues into ruminant sheep intestine resultedin 50-fold enhancement of SGLT1 expression.We aimedto determine if transport of sugar into the enterocytes is requiredfor SGLT1 induction, and delineate the signal-transduction pathways involved | Eur. J. Biochem. 270 3377-3388 2003 FEBS 2003 doi 10.1046 j.1432-1033.2003.03721.x Glucose sensing in the intestinal epithelium Jane Dyer1 Steven Vayro1 Timothy P. King2 and Soraya P. Shirazi-Beechey1 1 Epithelial Function and Development Group Department of Veterinary Preclinical Sciences University of Liverpool England UK 2Rowett Research Institute Aberdeen Scotland UK Dietary sugars regulate expression of the intestinal Na glucose cotransporter SGLT1 in many species. Using sheep intestine as a model we showed that lumenal monosaccharides both metabolisable and nonmetabolisable regulate SGLT1 expression. This regulation occurs not only at the level of transcription but also at the post-transcriptional level. Introduction of D-glucose and some D-glucose analogues into ruminant sheep intestine resulted in 50-oold enhancement of SGLT1 expression. We aimed to determine if transport of sugar into the enterocytes is required I or SGLT1 induction and delineate the signal-transduction pathways involved. A membrane impermeable D-glucose analogue di glucos-6-yl poly ethylene glycol 600 was synthesized and ìnl used into the intestines of ruminant sheep. SGLT1 expression was determined using transport studies Northern and Western blotting andimmunohistochemistry. An intestinal cell line STC-1 was used to mvettigate the signalling pathways. Intestinal infusion with di glucos-6-yl poly ethylene glycol 600 ledto induction of functional SGLT1 but the compound nid noh ínhibit Na glucose transport into intestinal brush-border membrane vesicles. Studies using cells showedthat increasedmedium glucose up-regulated SGLT1 abundance and SGLT1 promoter activity and increased i n r I aeel u Lllir I cAMP tenels. Glusonelindute d activation of the SGLT1 promoter was mimicked by th e proeeoi kinase A PKA agonist 8Br-cAMP and wss inhibned by H-89 a PKA inhibitor. Pertussis toxin a G-protein Gs -specific inhibitor enhanced SGLT1 psotein abunclnnee to levels observed 01recponee to glucoe 01 .