Journal
JOURNAL OF SURGICAL RESEARCH
Volume 167, Issue 1, Pages 56-61Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.jss.2010.04.026
Keywords
SGLT1; GLUT2; hexose transport; glucose uptake; intestinal absorption; protein kinase C
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Funding
- National Institutes of Health [DK39337-19]
- Mary E. Groff Foundation
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Introduction. Traditional models of intestinal glucose absorption confine GLUT2 to the basolateral membrane. Evidence suggests that GLUT2 is translocated to the apical membrane when the enterocyte is exposed to high luminal glucose concentrations. Hypothesis. GLUT2 translocates to the apical membrane by a PKC signaling mechanism dependent on activity of SGLT1 and the cellular cytostructure. Methods. Transporter-mediated glucose uptake was studied in rat jejunum using everted sleeves under seven conditions: Control, SGLT1 inhibition (phlorizin), GLUT2 inhibition (phloretin), both SGLT1 and GLUT2inhibition, PKC-inhibition (calphostin C or chelerythrine), and disruption of cellular cytostructure (nocodazole). Each condition was tested in iso-osmotic solutions of 1, 20, or 50 mM glucose for 1 or 5 min incubations (n = 6 rats each). Results. Control rats exhibited a saturable pattern of uptake at both durations of incubation. Phlorizin (P <= 0.006 each) inhibited markedly and phloretin (P <= 0.01 each) inhibited partially glucose uptake in all concentrations and time. Phloretin and phlorizin together completely inhibited uptake (P = 0.004 each). Calphostin C, chelerythrine, and nocodazole had little effect on glucose uptake at either 1 or 5 min. Inhibition of SGLT1 led to near complete cessation of transporter-mediated glucose uptake, while GLUT2 inhibition led to partial inhibition, suggesting some constitutive expression of GLUT2 in the apical membrane. Disruption of PKC signaling or cytoskeletal integrity partially inhibited transporter-mediated glucose uptake only in 1 mM glucose, suggesting a non-specific effect. Conclusions. Under these conditions, it does not appear that GLUT2 is translocated to the apical membrane on the cellular cytostructure in response to PKC signaling. (C) 2011 Elsevier Inc. All rights reserved.
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