Cited by 117Ion Transport and Channel RegulationMetabolism, Diabetes, and CancerDigestive system and related health

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Glucose sensing in the intestinal epithelium

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Dyer, Jane, Vayro, Steven, King, Timothy P., Shirazi‐Beechey, Soraya P.·2003·European Journal of Biochemistry

DOI 10.1046/j.1432-1033.2003.03721.x

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Abstract

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‐fold enhancement of SGLT1 expression. We aimed to determine if transport of sugar into the enterocytes is required for 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 infused into the intestines of ruminant sheep. SGLT1 expression was determined using transport studies, Northern and Western blotting, and immunohistochemistry. An intestinal cell line, STC‐1, was used to investigate the signalling pathways. Intestinal infusion with di(glucos‐6‐yl)poly(ethylene glycol) 600 led to induction of functional SGLT1, but the compound did not inhibit Na+/glucose transport into intestinal brush‐border membrane vesicles. Studies using cells showed that increased medium glucose up‐regulated SGLT1 abundance and SGLT1 promoter activity, and increased intracellular cAMP levels. Glucose‐induced activation of the SGLT1 promoter was mimicked by the protein kinase A (PKA) agonist, 8Br‐cAMP, and was inhibited by H‐89, a PKA inhibitor. Pertussis toxin, a G‐protein (G i)‐specific inhibitor, enhanced SGLT1 protein abundance to levels observed in response to glucose or 8Br‐cAMP. We conclude that lumenal glucose is sensed by a glucose sensor, distinct from SGLT1, residing on the external face of the lumenal membrane. The glucose sensor initiates a signalling pathway, involving a G‐protein‐coupled receptor linked to a cAMP–PKA pathway resulting in enhancement of SGLT1 expression.

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Authors: Dyer, J., Vayro, S., King, T. P., & Shirazi‐Beechey, S. P.
Affiliations: University of Liverpool (GB)
University of Aberdeen (GB)
ORCID: Shirazi‐Beechey, Soraya P.
Venue: European Journal of Biochemistry
Publisher: Wiley
Published: 2003-07-24
Volume: 270
Issue: 16
Pages: 3377-3388
ISSN: 0014-2956 (ISSN-L)
1432-1033
DOI: 10.1046/j.1432-1033.2003.03721.x
OpenAlex: W2054842789
Cited by: 117
References: 38
Citations by year: 2026: 1 · 2025: 2 · 2023: 5 · 2022: 3 · 2021: 4 · 2020: 5 · 2019: 5 · 2018: 6 · 2017: 5 · 2016: 4 · 2015: 1 · 2014: 5 · 2013: 1 · 2012: 9
FWCI: 1.72
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: European Journal of Biochemistry (publishedVersion)
PubMed (publishedVersion)
Funders: Wellcome Trust
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Health Sciences › Medicine › Gastroenterology › Digestive system and related health
Keywords: SGLT1, Na+/glucose cotransport, glucose sensor, cAMP/PKA signaling, G protein-coupled receptors, pertussis toxin, STC-1 cells, post-transcriptional regulation, monosaccharides
MeSH terms: Cyclic AMP, Animals, Female, Glucose, Glucosides, Intestinal Mucosa, Membrane Glycoproteins, Monosaccharide Transport Proteins, Polyethylene Glycols, Promoter Regions, Genetic, Receptors, Cell Surface, Sheep, Sodium, Cyclic AMP-Dependent Protein Kinases, Sodium-Glucose Transporter 1

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Glucose sensing in the intestinal epithelium

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