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Apical GLUT2 and Ca(v)1.3: regulation of rat intestinal glucose and calcium absorption

Morgan, E.L., Mace, O.J., Affleck, J. and Kellett, G.L. (2007) Apical GLUT2 and Ca(v)1.3: regulation of rat intestinal glucose and calcium absorption. Journal of Physiology, 580 (2). pp. 593-604. ISSN 0022-3751

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We have proposed a model of intestinal glucose absorption in which transport by SGLT1 induces rapid insertion and activation of GLUT2 in the apical membrane by a PKC II-dependent mechanism. Since PKC II requires Ca2+ and glucose is depolarizing, we have investigated whether glucose absorption is regulated by the entry of dietary Ca2+ through Cav1.3 in the apical membrane. When rat jejunum was perfused with 75 mM glucose, Ca2+-deplete conditions, or perfusion with the L-type antagonists nifedipine and verapamil strongly diminished the phloretin-sensitive apical GLUT2, but not the phloretin-insensitive SGLT1 component of glucose absorption. Western blotting showed that in each case there was a significant decrease in apical GLUT2 level, but no change in SGLT1 level. Inhibition of apical GLUT2 absorption coincided with inhibition of unidirectional 45Ca2+ entry by nifedipine and verapamil. At 10 mM luminal Ca2+, 45Ca2+ absorption in the presence of 75 mM glucose was 2- to 3-fold that in the presence of 75 mM mannitol. The glucose-induced component was SGLT1-dependent and nifedipine-sensitive. RT-PCR revealed the presence of Cav3 in jejunal mucosa; Western blotting and immunocytochemistry localized Cav3 to the apical membrane, together with Cav1.3. We conclude that in times of dietary sufficiency Cav1.3 may mediate a significant pathway of glucose-stimulated Ca2+ entry into the body and that luminal supply of Ca2+ is necessary for GLUT2-mediated glucose absorption. The integration of glucose and Ca2+ absorption represents a complex nutrient-sensing system, which allows both absorptive pathways to be regulated rapidly and precisely to match dietary intake.

Item Type: Article
Copyright, Publisher and Additional Information: Open access copy available from the journal web site.
Institution: The University of York
Academic Units: The University of York > Biology (York)
Depositing User: Open Access From Journal
Date Deposited: 23 Dec 2008 13:56
Last Modified: 23 Dec 2008 13:56
Published Version: http://dx.doi.org/10.1113/jphysiol.2006.124768
Status: Published
Publisher: Wiley-Blackwell
Refereed: Yes
Identification Number: 10.1113/jphysiol.2006.124768
URI: http://eprints.whiterose.ac.uk/id/eprint/5049

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