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Glucose sensing in the intestinal epithelium
Jane Dyer1, Steven Vayro, Timothy P King
1Epithelial Function and Development Group, Department of Veterinary Preclinical Sciences, University of Liverpool, England, UK.
European Journal of Biochemistry
|August 6, 2003
Summary
Dietary sugars regulate intestinal glucose transporter SGLT1 expression via a cell-surface sensor, not direct transport. This involves a G-protein-coupled receptor and cAMP-protein kinase A pathway, enhancing SGLT1 levels.
Area of Science:
- Physiology
- Molecular Biology
- Biochemistry
Background:
- Dietary sugars influence intestinal Na+/glucose cotransporter (SGLT1) expression in various species.
- Monosaccharides in the lumen regulate SGLT1 at both transcriptional and post-transcriptional levels.
- D-glucose introduction into sheep intestine enhances SGLT1 expression over 50-fold.
Purpose of the Study:
- To determine if sugar transport into enterocytes is necessary for SGLT1 induction.
- To identify the specific signal-transduction pathways involved in SGLT1 regulation.
- To investigate the role of a distinct lumenal glucose sensor.
Main Methods:
- Synthesized and infused a membrane-impermeable glucose analogue (di(glucos-6-yl)poly(ethylene glycol) 600) into sheep intestines.
- Assessed SGLT1 expression using transport studies, Northern/Western blotting, and immunohistochemistry.
- Utilized the STC-1 intestinal cell line to explore signaling pathways, including cAMP levels and protein kinase A (PKA) activity.
Main Results:
- Infusion of the impermeable glucose analogue induced functional SGLT1 without inhibiting Na+/glucose transport in vesicles.
- Increased medium glucose elevated SGLT1 abundance, promoter activity, and intracellular cAMP levels in STC-1 cells.
- Glucose-induced SGLT1 promoter activation was mimicked by a PKA agonist and blocked by a PKA inhibitor; pertussis toxin enhanced SGLT1 protein.
Conclusions:
- Lumenal glucose is detected by a sensor distinct from SGLT1 on the enterocyte's external membrane.
- This sensor triggers a signaling cascade involving a G-protein-coupled receptor and a cAMP-PKA pathway.
- The pathway ultimately enhances SGLT1 expression, independent of direct glucose transport into the cell.